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The time of administration of medicine is called as ‘Aushadhasevana kala’. The efficacy and safety of medicine vary as per the time of administration. Chrono-pharmacology deals with studies of biological rhythm dependencies of drugs regarding its pharmacological effects and/or pharmacokinetics/dynamics of drugs in both animals and humans.
In Ayurveda, different times of medicine administration are mentioned for pacification (shamana) therapies. [A.Hr.Sutra Sthana.13]<ref name= Hridaya > Vagbhata. Ashtanga Hridayam. Edited by Harishastri Paradkar Vaidya. 1st ed. Varanasi: Krishnadas Academy;2000.</ref> The principle of circadian rhythm of [[dosha]], their influence on human physiology is considered to achieve highest active potential of a medicine. By applying this principle of chronopharmacology, maximum efficacy can be achieved even in smaller doses. Moreover, a single medicine can be used in different disorders as per biological rhythms and states of [[dosha]]. Thus, the requirement of medicine can be reduced to treat multiple disorders. Duration of medical treatment in chronic disorders can also be reduced.
It is to be noted that in clinical practice, only gastrointestinal irritation and drug-food interactions are considered while deciding the time of administration. Accordingly the drug is prescribed to take empty stomach or after meals. However, the principles of chronopharmacology in regards to biological rhythm are not followed.
The interactions between the external environment and its influence on human biology is less known to contemporary medical science. Change in time, day-night cycle can influence human physiological functions. Accordingly, this may affect absorption and metabolism of a drug. The principles of chrono-pharmacology can provide significant inputs to improve safety and efficacy profiles of drugs. More research studies are needed to establish principles of chrono-pharmacology in current clinical practice. It is still a developing science in today's era. However, ayurvedic rishis have known about it for thousands of years.
This article describes the time of administration of medicine and its application in clinical practice.
{{Infobox
|title = Contributors
|label1 = Section/Chapter
|data1 = [[Chikitsa]] / [[Aushadhasevana kala]]
|label2 = Authors
|data2 = Aneesh E.G., Deole Y.S.
|label3 = Reviewed by
|data3 = Basisht G.
|label4 = Affiliations
|data4 = [[Charak Samhita Research, Training and Development Centre]], I..T.R.A., Jamnagar
|label5 = Correspondence email:
|data5 = carakasamhita@gmail.com
|label6 = Date of publication
|data6 = May 21, 2021
|label7 = DOI
|data7 = Awaited
}}
==Synonyms==
It is also known as bheshajakala.
==Times of administration of medicine==
Ten variable times of administration of medicine are described in Ayurveda.
#Empty stomach or early morning
#Before food
#After food
#In between food
#Before and after food
#Along with food
#Along with each morsel
#In between two morsels
#Frequent
#Bed time at night
===Empty stomach===
'''Synonyms:'''Pratahaniranna, abhaktam, ananna
'''Time:''' Administration of medicine early in the morning empty stomach, or during sunrise [Sha.Purvakhanda.2/2]<ref name= Shargadara> Sharangadhara. Sharangadhara Samhita. Translated from Sanskrit by K.R. Srikantha Murthy. Reprint ed. Varanasi: Chaukhambha orientalia;2016.</ref> or when the stomach is free from [[kapha]][[dosha]] at the time of breakfast (7.30AM-8.30AM). [A.S.Sutra Sthana.23/14]<ref name= Sangraha> Vridha Vagbhata, Ashtanga Sangraha. Edited by Shivaprasad Sharma. 3rd ed. Varanasi: Chaukhamba sanskrit series office;2012.</ref>
'''Implications:'''The efficacy of medicine is more significant at this time on empty stomach. The therapeutic vomiting and purgative drugs are administered at this time and weight reduction can be achieved.[Sha.Purvakhanda.2/4]<ref name=Shargadara/>The person with good strength shall take medicine at this time. [Ka.Khila Sthana 3/45]<ref name=Kashyapa> Kashyapa. Kashyapa Samhita. Edited by P. V. Tewari. Reprint. Varanasi: Chaukhambha vishvabharati;2008.</ref> Medicines for the treatment of aggravated [[kapha]] and [[pitta]] conditions are given at this time. [Sha.Purvakhanda.2/4]<ref name=Shargadara/>This time is best for treating disorders due to vitiation of vyana[[vata]].[Cha.Sa.[[Chikitsa Sthana]]30/299]
'''Contraindications:''' The medicine with higher potency shall not be administered on empty stomach to children, aged persons; ladies, debilitated persons. The medicine given at this time may cause tiredness and weakness. [Su.Sa.Uttara Sthana.64/67]<ref name= Susruta> Sushruta. Sushruta Samhita. Edited by Jadavaji Trikamji Aacharya. 8th ed. Varanasi: Chaukhambha Orientalia;2005.</ref> Persons who are thirsty, hungry, who have consumed cold water, suffering from indigestion shall not take medicine at this time. [A.S.Sutra Sthana.23/23]<ref name=Sangraha/>
===Before meals===
'''Synonyms:'''Bhuktadau, prakbaktam, purvabhakta, annadau
'''Implications:''' The medicine is properly digested without being expelled when ingested empty stomach. It cures diseases due to the vitiation of apana[[vata]] and the lower part of body. It strengthens the lower part of body. This time is ideal to administer medicine for reducing weight. [A.S.Sutra Sthana. 23/15]<ref name=Sangraha/>[Cha.Sa.[[Chikitsa Sthana]]30/299], [Sha.Purvakhanda.2/5]<ref name=Shargadara/>The [[dosha]] present in the stomach (amasaya) is destroyed if medicine is given at this time. [Ka.Khila Sthana 3/44]<ref name=Kashyapa/>
'''Indications:''' Aged persons, children, ladies and cowards. [Su.Sa.Uttara Sthana.64/69]<ref name=Susruta/>
===After meals===
'''Synonyms:''' Bhuktapashchat, adhobhaktam, adhabhaktam, bhuktaante
'''Implications:''' The medicine interacts with food present in the stomach. The medicine is mixed and circulated with the nourishing part prepared from food (ahara rasa) by vyana[[vata]]. This time of administration is indicated in diseases of upper part of body as it provides strength to upper part of body. [Su.Sa.Uttara Sthana.64/72]<ref name=Susruta/>[A.S.Sutra Sthana.23/17]<ref name=Sangraha/> It pacifies the diseases of chest, throat and head immediately.[Ka. Khila Sthana 3/47]<ref name=Kashyapa/> It improves the stoutness of body. [A.S.Sutra Sthana 23/17]<ref name=Sangraha/> Medicine is given after breakfast or lunch in diseases due to vitiation of vyana[[vata]][Cha.Sa.[[Chikitsa Sthana]] 30/299], [Sha.Purvakhanda.2/7]<ref name=Shargadara/>[A.Hr.Sutra Sthana.13/39]<ref name=Hridaya/>[A.S.Sutra Sthana 23/17]<ref name=Sangraha/> Medicine is given after dinner or evening meals in diseases due to vitiation of udana[[vata]].[A.Hr.Sutra Sthana 13/39]<ref name=Hridaya/>, [A.S.Sutra Sthana 23/17]<ref name=Sangraha/> Sharangadhara advises to give medicines after evening food to treat disorders due to prana vayu [Sha.Purvakhanda 02/10]<ref name=Shargadara/> and disorders of [[kapha]][[dosha]]. [A.S.Sutra Sthana 23/17]<ref name=Sangraha/>
===During meals, after finishing first half of meal===
'''Synonyms:''' Bhuktamadhya, madhya bhaktam, madhye.
'''Implications:''' The medicine is given to improve digestion in persons with poor digestive capacity. [Sha.Purvakhanda.2/6]<ref name=Shargadara/> It improves the functions of samana[[vata]] and digestive processes. [Sha.Purvakhanda 2/6]<ref name=Shargadara/>[Cha.Sa.[[Chikitsa Sthana]] 30/299] [A.Hr.Sutra Sthana.13/38]<ref name=Hridaya/>[A.S.Sutra Sthana 23/16]<ref name=Sangraha/> This time is indicated in diseases of middle part of body. [Su.Sa.Uttara Sthana.64/72]<ref name=Susruta/> The medicine during meals interacts with food and digestive juices in gut. It can easily move the [[dosha]] in internal organs (antaraashaya). [Ka.Khila Sthana 3/47]<ref name=Kashyapa/> It cures the diseases due to [[pitta]] [[dosha]] and those related to gut.[A.S.Sutra Sthana 23/16]<ref name=Sangraha/>
===Before and after meals (samudgam)===
In two doses before and after meals
'''Implications:''' This time is best suited to give medicine to treat hiccups, tremors, and convulsions.[Sha.Purvakhanda.2/7]<ref name=Shargadara/>, [A.Hr. Sutra Sthana 13/41]<ref name=Hridaya/> The medicine should be given along with light meal and meal in less quantity. [A.S.Sutra Sthana.23/20]<ref name=Sangraha/> [Cha.Sa.[[Chikitsa Sthana]]30/301] The time of medicine is indicated to treat [[dosha]] that has spread in upper and lower directions. [Su.Sa.Uttara Sthana.64/77]<ref name=Susruta/>[Ka.Khila Sthana 3/48]<ref name=Kashyapa/>, [A.S.Sutra Sthana.23/20]<ref name=Sangraha/>
===Medicine mixed with food===
'''Synonyms:''' Annaihiyuktam, sabhaktam, saannam,bhaktasamyuktam
'''Implications:''' Medicines are given by mixing with variety of attractive foods. [Cha.Sa.[[Chikitsa Sthana]]30/301] This time of medicine is used to treat anorexia [Sha.Purvakhanda.2/5]<ref name=Shargadara/> and persons with good or low strength, who have aversion towards medicine, children and aged persons.[Su.Sa.Uttara Sthana.64/75]<ref name=Susruta/> This form is also used when the patient is not willing to take essential medicines. The medicine given at this time nourishes body. It helps to protect the strength and digestive capacity. It is used to treat the diseases affecting the whole body. [A.S.Sutra Sthana.23/18]<ref name=Sangraha/> It is indicated in persons with poor digestion, ladies, delicate, wounded, and weak individuals.[Ka.Khila Sthana 3/49]<ref name=Kashyapa/>
===Mixed with each morsel of food===
'''Synonyms:'''Grasa, grasegrase, sagrasam
'''Implications:''' Medicines at this time are indicated in disorders due to vitiation of prana [[vata]].[Cha.Sa.[[Chikitsa Sthana]] 30/300] [A.Hr.Sutra Sthana.13/39]<ref name=Hridaya/>[A.S.Sutra Sthana 23/22]<ref name=Sangraha/> Aphrodisiac (vajeekarana) medicines and those for increasing the digestive capacity are administered by adding with each morsel of food. [Ka.Khila Sthana 3/50]<ref name=Kashyapa/>[A.S.Sutra Sthana 23/22]<ref name=Sangraha/> Sharangadhara advises this time of medicine to treat disorders of udaana[[vata]]. [Sha.Purva Khanda 2/10]<ref name=Shargadara/>
'''Indications:''' Weak persons, persons having poor spermatogenesis and debility (ksheena shukra), scanty semen (alpa shukra) [Ka.Khila Sthana 3/50]<ref name=Kashyapa/>, less digestive capacity [Su.Sa.Uttara Sthana 64/82]<ref name=Susruta/>, disorders of speech (swarabhanga) and diseases related to throat. [Sha.Purvakhanda 2/10]<ref name=Shargadara/>
===In between two morsels===
'''Synonyms:''' Grasaantare, kavalantare
'''Implications:''' This time of medicine is indicated when emetic medicine needs to be given with food. Emetic smoke inhalation is given at this time to treat conditions of dyspnea.[Su.Sa.Uttara Sthana 64/82]<ref name=Susruta/> Medicines for cardiac diseases, drugs for therapeutic vomiting and medicated smoke are given at this time. [A.S.Sutra Sthana 23/22]<ref name=Sangraha/> It is also indicated in impaired voice (swarabhanga) and throat disorders. [Sha.Purvakhanda 2/10]<ref name=Shargadara/> This time is indicated for diseases due to vitiation of vyana[[vata]]. [A.S.Sutra Sthana.23/19]<ref name=Sangraha/>
===Frequent administration or as needed===
'''Synonyms:''' Muhurmuhu, muhuhu
'''Implications:''' This time of medicine is used to treat recurrent bouts of diseases like morbid thirst (trit), vomiting (chhardi), hiccups (hikka), dyspnea (shwasa), cough (kasa) and poisoning (garavisha). The medicines can be given with or without food.[Sha.Purvakhanda 2/11]<ref name=Shargadara/> [Cha.Sa.[[Chikitsa Sthana]] 30/300],[Su.Sa.Uttara Sthana 64/79]<ref name=Susruta/>,[Ka.Khila Sthana 3/48]<ref name=Kashyapa/>, [A.Hr.Sutra Sthana 13/40]<ref name=Hridaya/>,[A.S.Sutra Sthana 23/21]<ref name=Sangraha/>
===Bed time (nishi)===
'''Implications:''' This time is indicated to treat the diseases of head and neck.[Sha.Purvakhanda 2/12]<ref name=Shargadara/>, [A.Hr.Sutra Sthana 13/41]<ref name=Hridaya/>, [A.S.Sutra Sthana 23/22]<ref name=Sangraha/> It is also indicated to treat psychiatric diseases. The medicines in different forms are given for reducing body bulk (lekhana), nourishing ([[brimhana]]), digestive ([[pachana]]) and pacifying (shamana) purpose.
===In between two meals===
(If meals are taken in morning and evening, then medicine is given in afternoon)
'''Synonyms:''' Antarabhaktam, bhaktasyamadhyam
'''Implications:''' This time is indicated when the digestion of food is complete. It is indicated for those having good digestive capacity [A.S.Sutra Sthana.23/19]<ref name=Sangraha/> and persons suffering from mild diseases.[Ka.Khila Sthana 3/49]<ref name=Kashyapa/> The medicine given at this time is good for heart (hridya), gives more strength to mind (manobalakara), increases the digestive capacity ([[deepana]]) and wholesome (pathya).[Su.Sa.Uttara Sthana.64/75]<ref name=Susruta/>
==Factors for deciding time of administration==
The time of administration depends on following factors.
#Biological rhythm of [[dosha]] at that time and its role in pathogenesis of disease
#Food and drug interactions, presence of food, digestive juices in stomach that can interfere with efficacy of drug
#[[Vata]][[dosha]] is responsible for transport of medicine to the receptor site. Type of [[vata]][[dosha]] involved in pathogenesis of disease is considered.
#Form of medicine that can achieve highest efficacy at that time.
#Age, physiological condition of person like pregnancy, lactation etc., strength of person.
==Time of administration based on form of medicine==
*Empty stomach: Decoction [Sha.Purvakhanda.2/3]<ref name=Shargadara/>
*Before and after meals: Electuaries (avaleha) for digestion ([[pachana]])
*With each morsel: Medicines in powder, electuary and tablet form. [A.S.Sutra Sthana.23/22]<ref name=Sangraha/>
*In between two morsel: Electuaries [Su.Sa.Uttara Sthana.64/82]<ref name=Susruta/>
==Contemporary views and current researches==
The study of variable effects of drugs given at different times influenced by biological rhythms is called chrono-pharmacology. The drugs administered at different timings show different activity profiles. Their action, absorption, metabolism and excretion are influenced by the circadian rhythms and body states at different timings.
It is reported that the absorption of diclofenac was significantly low, if administered in the evening as compared with the morning dosage. It also shows a delay in absorption for the evening dosage. After overnight fasting, the absorption of paracetamol is five times more than when ingested after a high carbohydrate diet.<ref>McGilveray, I. J. & Mattok, G. L. (1972). Some factors affecting the absorption of paracetamol. J.Pharm. Pharmac., 24, 615-619.</ref> The drug flurbiprofen is more effective if given in the morning than evening. It showed more significant activity in improving the symptoms like pain and spinal flexibility in rheumatoid arthritis patients. This indicates that the time of drug administration influences therapeutic efficacy.<ref>Pownall R, Pickvance NJ. The optimum interval between flurbiprofen doses--scheduling for circadian rhythms in rheumatoid arthritis. Br J Clin Pract. 1987;41(4):689-693.</ref>
For certain drugs, the time of administration is as important as the dose and route of administration. Lipophilic drugs are absorbed faster in the morning as compared to the evening. Gastric acid secretion, gastric pH, gastric motility, gastric emptying time and gastric blood flow vary according to time of the day. These factors might have an impact over the absorption of drug.<ref>Pinar Erkekoglu, Terken Baydar. Chronopharmacokinectics of drugs in toxicological aspects: A short review for pharmacy practitioners. J Res Pharm Pract. 2012 Jul-Sep; 1(1): 3–9.doi: 10.4103/2279-042X.99670</ref> A large number of drugs like analgesics, antibiotics, antitumor drugs, immunosuppressive agents, cardio vascular drugs, antidepressants show varying potency and disposition in kinetics based on the time of drug administration.<ref>Zhang C, Yu Z, Li X, Xu Y, Liu D (2014) Chronopharmacodynamics and Chronopharmacokinetics of Pethidine in Mice. PLoS ONE 9(7): e102054. doi:10.1371/journal.pone.0102054</ref>
The research on time of administration of drugs in conventional medicine in connection with the principles described in Ayurveda may provide significant inputs to reduce dosage, duration of treatment, and higher efficacy with less toxic effects.
==List of theses done==
#Srividhya H Iyer (2003). Concept of Bhaishajyakaala and its applicability in relation to agni w.s.r to Amlapitta. Department of Basic Principles. IPGT&RA Jamnagar
==More information==
[[Yonivyapat Chikitsa]]
==Abbreviations==
Cha. = Charak, Su. = Sushruta, A. = Ashtanga, S. = Sangraha, Hr. = Hridaya, Sa. = Samhita, Ka. = Kasyapa, Sha. = Shargadara
==References==
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|title=Aushadhasevana kala
|titlemode=append
|keywords=carakasamhitaonline, charak samhita, caraka samhita, ayurveda, Aushadhasevana kala, time of administration of medicine, Chrono-pharmacology, indian systems of medcine, natural medicine, therapy
|description=The time of administration of medicine is called as Aushadhasevana kala
|image=http://www.carakasamhitaonline.com/resources/assets/ogimgs.jpg
|image_alt=carak samhita
|type=article
}}
<div style='text-align:justify;'>
The time of administration of medicine is called as ‘Aushadhasevana kala’. The efficacy and safety of medicine vary as per the time of administration. Chrono-pharmacology deals with studies of biological rhythm dependencies of drugs regarding its pharmacological effects and/or pharmacokinetics/dynamics of drugs in both animals and humans.
In Ayurveda, different times of medicine administration are mentioned for pacification (shamana) therapies. [A.Hr.Sutra Sthana.13]<ref name= Hridaya > Vagbhata. Ashtanga Hridayam. Edited by Harishastri Paradkar Vaidya. 1st ed. Varanasi: Krishnadas Academy;2000.</ref> The principle of circadian rhythm of [[dosha]], their influence on human physiology is considered to achieve highest active potential of a medicine. By applying this principle of chronopharmacology, maximum efficacy can be achieved even in smaller doses. Moreover, a single medicine can be used in different disorders as per biological rhythms and states of [[dosha]]. Thus, the requirement of medicine can be reduced to treat multiple disorders. Duration of medical treatment in chronic disorders can also be reduced.
It is to be noted that in clinical practice, only gastrointestinal irritation and drug-food interactions are considered while deciding the time of administration. Accordingly the drug is prescribed to take empty stomach or after meals. However, the principles of chronopharmacology in regards to biological rhythm are not followed.
The interactions between the external environment and its influence on human biology is less known to contemporary medical science. Change in time, day-night cycle can influence human physiological functions. Accordingly, this may affect absorption and metabolism of a drug. The principles of chrono-pharmacology can provide significant inputs to improve safety and efficacy profiles of drugs. More research studies are needed to establish principles of chrono-pharmacology in current clinical practice. It is still a developing science in today's era. However, ayurvedic rishis have known about it for thousands of years.
This article describes the time of administration of medicine and its application in clinical practice.
{{Infobox
|title = Contributors
|label1 = Section/Chapter
|data1 = [[Chikitsa]] / [[Aushadhasevana kala]]
|label2 = Authors
|data2 = Aneesh E.G., Deole Y.S.
|label3 = Reviewed by
|data3 = Basisht G.
|label4 = Affiliations
|data4 = [[Charak Samhita Research, Training and Development Centre]], I..T.R.A., Jamnagar
|label5 = Correspondence email:
|data5 = carakasamhita@gmail.com
|label6 = Date of publication
|data6 = May 21, 2021
|label7 = DOI
|data7 = Awaited
}}
==Synonyms==
It is also known as bheshajakala.
==Times of administration of medicine==
Ten variable times of administration of medicine are described in Ayurveda.
#Empty stomach or early morning
#Before food
#After food
#In between food
#Before and after food
#Along with food
#Along with each morsel
#In between two morsels
#Frequent
#Bed time at night
===Empty stomach===
'''Synonyms:'''Pratahaniranna, abhaktam, ananna
'''Time:''' Administration of medicine early in the morning empty stomach, or during sunrise [Sha.Purvakhanda.2/2]<ref name= Shargadara> Sharangadhara. Sharangadhara Samhita. Translated from Sanskrit by K.R. Srikantha Murthy. Reprint ed. Varanasi: Chaukhambha orientalia;2016.</ref> or when the stomach is free from [[kapha]][[dosha]] at the time of breakfast (7.30AM-8.30AM). [A.S.Sutra Sthana.23/14]<ref name= Sangraha> Vridha Vagbhata, Ashtanga Sangraha. Edited by Shivaprasad Sharma. 3rd ed. Varanasi: Chaukhamba sanskrit series office;2012.</ref>
'''Implications:'''The efficacy of medicine is more significant at this time on empty stomach. The therapeutic vomiting and purgative drugs are administered at this time and weight reduction can be achieved.[Sha.Purvakhanda.2/4]<ref name=Shargadara/>The person with good strength shall take medicine at this time. [Ka.Khila Sthana 3/45]<ref name=Kashyapa> Kashyapa. Kashyapa Samhita. Edited by P. V. Tewari. Reprint. Varanasi: Chaukhambha vishvabharati;2008.</ref> Medicines for the treatment of aggravated [[kapha]] and [[pitta]] conditions are given at this time. [Sha.Purvakhanda.2/4]<ref name=Shargadara/>This time is best for treating disorders due to vitiation of vyana[[vata]].[Cha.Sa.[[Chikitsa Sthana]]30/299]
'''Contraindications:''' The medicine with higher potency shall not be administered on empty stomach to children, aged persons; ladies, debilitated persons. The medicine given at this time may cause tiredness and weakness. [Su.Sa.Uttara Sthana.64/67]<ref name= Susruta> Sushruta. Sushruta Samhita. Edited by Jadavaji Trikamji Aacharya. 8th ed. Varanasi: Chaukhambha Orientalia;2005.</ref> Persons who are thirsty, hungry, who have consumed cold water, suffering from indigestion shall not take medicine at this time. [A.S.Sutra Sthana.23/23]<ref name=Sangraha/>
===Before meals===
'''Synonyms:'''Bhuktadau, prakbaktam, purvabhakta, annadau
'''Implications:''' The medicine is properly digested without being expelled when ingested empty stomach. It cures diseases due to the vitiation of apana[[vata]] and the lower part of body. It strengthens the lower part of body. This time is ideal to administer medicine for reducing weight. [A.S.Sutra Sthana. 23/15]<ref name=Sangraha/>[Cha.Sa.[[Chikitsa Sthana]]30/299], [Sha.Purvakhanda.2/5]<ref name=Shargadara/>The [[dosha]] present in the stomach (amasaya) is destroyed if medicine is given at this time. [Ka.Khila Sthana 3/44]<ref name=Kashyapa/>
'''Indications:''' Aged persons, children, ladies and cowards. [Su.Sa.Uttara Sthana.64/69]<ref name=Susruta/>
===After meals===
'''Synonyms:''' Bhuktapashchat, adhobhaktam, adhabhaktam, bhuktaante
'''Implications:''' The medicine interacts with food present in the stomach. The medicine is mixed and circulated with the nourishing part prepared from food (ahara rasa) by vyana[[vata]]. This time of administration is indicated in diseases of upper part of body as it provides strength to upper part of body. [Su.Sa.Uttara Sthana.64/72]<ref name=Susruta/>[A.S.Sutra Sthana.23/17]<ref name=Sangraha/> It pacifies the diseases of chest, throat and head immediately.[Ka. Khila Sthana 3/47]<ref name=Kashyapa/> It improves the stoutness of body. [A.S.Sutra Sthana 23/17]<ref name=Sangraha/> Medicine is given after breakfast or lunch in diseases due to vitiation of vyana[[vata]][Cha.Sa.[[Chikitsa Sthana]] 30/299], [Sha.Purvakhanda.2/7]<ref name=Shargadara/>[A.Hr.Sutra Sthana.13/39]<ref name=Hridaya/>[A.S.Sutra Sthana 23/17]<ref name=Sangraha/> Medicine is given after dinner or evening meals in diseases due to vitiation of udana[[vata]].[A.Hr.Sutra Sthana 13/39]<ref name=Hridaya/>, [A.S.Sutra Sthana 23/17]<ref name=Sangraha/> Sharangadhara advises to give medicines after evening food to treat disorders due to prana vayu [Sha.Purvakhanda 02/10]<ref name=Shargadara/> and disorders of [[kapha]][[dosha]]. [A.S.Sutra Sthana 23/17]<ref name=Sangraha/>
===During meals, after finishing first half of meal===
'''Synonyms:''' Bhuktamadhya, madhya bhaktam, madhye.
'''Implications:''' The medicine is given to improve digestion in persons with poor digestive capacity. [Sha.Purvakhanda.2/6]<ref name=Shargadara/> It improves the functions of samana[[vata]] and digestive processes. [Sha.Purvakhanda 2/6]<ref name=Shargadara/>[Cha.Sa.[[Chikitsa Sthana]] 30/299] [A.Hr.Sutra Sthana.13/38]<ref name=Hridaya/>[A.S.Sutra Sthana 23/16]<ref name=Sangraha/> This time is indicated in diseases of middle part of body. [Su.Sa.Uttara Sthana.64/72]<ref name=Susruta/> The medicine during meals interacts with food and digestive juices in gut. It can easily move the [[dosha]] in internal organs (antaraashaya). [Ka.Khila Sthana 3/47]<ref name=Kashyapa/> It cures the diseases due to [[pitta]] [[dosha]] and those related to gut.[A.S.Sutra Sthana 23/16]<ref name=Sangraha/>
===Before and after meals (samudgam)===
In two doses before and after meals
'''Implications:''' This time is best suited to give medicine to treat hiccups, tremors, and convulsions.[Sha.Purvakhanda.2/7]<ref name=Shargadara/>, [A.Hr. Sutra Sthana 13/41]<ref name=Hridaya/> The medicine should be given along with light meal and meal in less quantity. [A.S.Sutra Sthana.23/20]<ref name=Sangraha/> [Cha.Sa.[[Chikitsa Sthana]]30/301] The time of medicine is indicated to treat [[dosha]] that has spread in upper and lower directions. [Su.Sa.Uttara Sthana.64/77]<ref name=Susruta/>[Ka.Khila Sthana 3/48]<ref name=Kashyapa/>, [A.S.Sutra Sthana.23/20]<ref name=Sangraha/>
===Medicine mixed with food===
'''Synonyms:''' Annaihiyuktam, sabhaktam, saannam,bhaktasamyuktam
'''Implications:''' Medicines are given by mixing with variety of attractive foods. [Cha.Sa.[[Chikitsa Sthana]]30/301] This time of medicine is used to treat anorexia [Sha.Purvakhanda.2/5]<ref name=Shargadara/> and persons with good or low strength, who have aversion towards medicine, children and aged persons.[Su.Sa.Uttara Sthana.64/75]<ref name=Susruta/> This form is also used when the patient is not willing to take essential medicines. The medicine given at this time nourishes body. It helps to protect the strength and digestive capacity. It is used to treat the diseases affecting the whole body. [A.S.Sutra Sthana.23/18]<ref name=Sangraha/> It is indicated in persons with poor digestion, ladies, delicate, wounded, and weak individuals.[Ka.Khila Sthana 3/49]<ref name=Kashyapa/>
===Mixed with each morsel of food===
'''Synonyms:'''Grasa, grasegrase, sagrasam
'''Implications:''' Medicines at this time are indicated in disorders due to vitiation of prana [[vata]].[Cha.Sa.[[Chikitsa Sthana]] 30/300] [A.Hr.Sutra Sthana.13/39]<ref name=Hridaya/>[A.S.Sutra Sthana 23/22]<ref name=Sangraha/> Aphrodisiac (vajeekarana) medicines and those for increasing the digestive capacity are administered by adding with each morsel of food. [Ka.Khila Sthana 3/50]<ref name=Kashyapa/>[A.S.Sutra Sthana 23/22]<ref name=Sangraha/> Sharangadhara advises this time of medicine to treat disorders of udaana[[vata]]. [Sha.Purva Khanda 2/10]<ref name=Shargadara/>
'''Indications:''' Weak persons, persons having poor spermatogenesis and debility (ksheena shukra), scanty semen (alpa shukra) [Ka.Khila Sthana 3/50]<ref name=Kashyapa/>, less digestive capacity [Su.Sa.Uttara Sthana 64/82]<ref name=Susruta/>, disorders of speech (swarabhanga) and diseases related to throat. [Sha.Purvakhanda 2/10]<ref name=Shargadara/>
===In between two morsels===
'''Synonyms:''' Grasaantare, kavalantare
'''Implications:''' This time of medicine is indicated when emetic medicine needs to be given with food. Emetic smoke inhalation is given at this time to treat conditions of dyspnea.[Su.Sa.Uttara Sthana 64/82]<ref name=Susruta/> Medicines for cardiac diseases, drugs for therapeutic vomiting and medicated smoke are given at this time. [A.S.Sutra Sthana 23/22]<ref name=Sangraha/> It is also indicated in impaired voice (swarabhanga) and throat disorders. [Sha.Purvakhanda 2/10]<ref name=Shargadara/> This time is indicated for diseases due to vitiation of vyana[[vata]]. [A.S.Sutra Sthana.23/19]<ref name=Sangraha/>
===Frequent administration or as needed===
'''Synonyms:''' Muhurmuhu, muhuhu
'''Implications:''' This time of medicine is used to treat recurrent bouts of diseases like morbid thirst (trit), vomiting (chhardi), hiccups (hikka), dyspnea (shwasa), cough (kasa) and poisoning (garavisha). The medicines can be given with or without food.[Sha.Purvakhanda 2/11]<ref name=Shargadara/> [Cha.Sa.[[Chikitsa Sthana]] 30/300],[Su.Sa.Uttara Sthana 64/79]<ref name=Susruta/>,[Ka.Khila Sthana 3/48]<ref name=Kashyapa/>, [A.Hr.Sutra Sthana 13/40]<ref name=Hridaya/>,[A.S.Sutra Sthana 23/21]<ref name=Sangraha/>
===Bed time (nishi)===
'''Implications:''' This time is indicated to treat the diseases of head and neck.[Sha.Purvakhanda 2/12]<ref name=Shargadara/>, [A.Hr.Sutra Sthana 13/41]<ref name=Hridaya/>, [A.S.Sutra Sthana 23/22]<ref name=Sangraha/> It is also indicated to treat psychiatric diseases. The medicines in different forms are given for reducing body bulk (lekhana), nourishing ([[brimhana]]), digestive ([[pachana]]) and pacifying (shamana) purpose.
===In between two meals===
(If meals are taken in morning and evening, then medicine is given in afternoon)
'''Synonyms:''' Antarabhaktam, bhaktasyamadhyam
'''Implications:''' This time is indicated when the digestion of food is complete. It is indicated for those having good digestive capacity [A.S.Sutra Sthana.23/19]<ref name=Sangraha/> and persons suffering from mild diseases.[Ka.Khila Sthana 3/49]<ref name=Kashyapa/> The medicine given at this time is good for heart (hridya), gives more strength to mind (manobalakara), increases the digestive capacity ([[deepana]]) and wholesome (pathya).[Su.Sa.Uttara Sthana.64/75]<ref name=Susruta/>
==Factors for deciding time of administration==
The time of administration depends on following factors.
#Biological rhythm of [[dosha]] at that time and its role in pathogenesis of disease
#Food and drug interactions, presence of food, digestive juices in stomach that can interfere with efficacy of drug
#[[Vata]][[dosha]] is responsible for transport of medicine to the receptor site. Type of [[vata]][[dosha]] involved in pathogenesis of disease is considered.
#Form of medicine that can achieve highest efficacy at that time.
#Age, physiological condition of person like pregnancy, lactation etc., strength of person.
==Time of administration based on form of medicine==
*Empty stomach: Decoction [Sha.Purvakhanda.2/3]<ref name=Shargadara/>
*Before and after meals: Electuaries (avaleha) for digestion ([[pachana]])
*With each morsel: Medicines in powder, electuary and tablet form. [A.S.Sutra Sthana.23/22]<ref name=Sangraha/>
*In between two morsel: Electuaries [Su.Sa.Uttara Sthana.64/82]<ref name=Susruta/>
==Contemporary views and current researches==
The study of variable effects of drugs given at different times influenced by biological rhythms is called chrono-pharmacology. The drugs administered at different timings show different activity profiles. Their action, absorption, metabolism and excretion are influenced by the circadian rhythms and body states at different timings.
It is reported that the absorption of diclofenac was significantly low, if administered in the evening as compared with the morning dosage. It also shows a delay in absorption for the evening dosage. After overnight fasting, the absorption of paracetamol is five times more than when ingested after a high carbohydrate diet.<ref>McGilveray, I. J. & Mattok, G. L. (1972). Some factors affecting the absorption of paracetamol. J.Pharm. Pharmac., 24, 615-619.</ref> The drug flurbiprofen is more effective if given in the morning than evening. It showed more significant activity in improving the symptoms like pain and spinal flexibility in rheumatoid arthritis patients. This indicates that the time of drug administration influences therapeutic efficacy.<ref>Pownall R, Pickvance NJ. The optimum interval between flurbiprofen doses--scheduling for circadian rhythms in rheumatoid arthritis. Br J Clin Pract. 1987;41(4):689-693.</ref>
For certain drugs, the time of administration is as important as the dose and route of administration. Lipophilic drugs are absorbed faster in the morning as compared to the evening. Gastric acid secretion, gastric pH, gastric motility, gastric emptying time and gastric blood flow vary according to time of the day. These factors might have an impact over the absorption of drug.<ref>Pinar Erkekoglu, Terken Baydar. Chronopharmacokinectics of drugs in toxicological aspects: A short review for pharmacy practitioners. J Res Pharm Pract. 2012 Jul-Sep; 1(1): 3–9.doi: 10.4103/2279-042X.99670</ref> A large number of drugs like analgesics, antibiotics, antitumor drugs, immunosuppressive agents, cardio vascular drugs, antidepressants show varying potency and disposition in kinetics based on the time of drug administration.<ref>Zhang C, Yu Z, Li X, Xu Y, Liu D (2014) Chronopharmacodynamics and Chronopharmacokinetics of Pethidine in Mice. PLoS ONE 9(7): e102054. doi:10.1371/journal.pone.0102054</ref>
The research on time of administration of drugs in conventional medicine in connection with the principles described in Ayurveda may provide significant inputs to reduce dosage, duration of treatment, and higher efficacy with less toxic effects.
==List of theses done==
#Srividhya H Iyer (2003). Concept of Bhaishajyakaala and its applicability in relation to agni w.s.r to Amlapitta. Department of Basic Principles. IPGT&RA Jamnagar
==More information==
[[Yonivyapat Chikitsa]]
==Abbreviations==
Cha. = Charak, Su. = Sushruta, A. = Ashtanga, S. = Sangraha, Hr. = Hridaya, Sa. = Samhita, Ka. = Kasyapa, Sha. = Shargadara
==References==
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