| Title | Time dependency in experimental and clinical pharmacokinetics | |
| Author | Charalampos T. Plessas¹,², Achilles Benakis¹, Costas Sekeris³ and Stavros T. Plessas²,⁴
1. Laboratory of Drug Metabolism, Department of Pharmacology, University of Geneva, Geneva, Switzerland 2. PHARMAKON-Press Information Services, Athens, Greece 3. Department of Biochemistry, University of Athens and Biological Research Center, The National Hellenic Research Foundation, Athens, Greece 4. Institute of Technological Education, Ministry of National Education, Athens, Greece |
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| Citation | Plessas, C.T., Benakis, A., Sekeris, C., Plessas, S.T.: Time dependency in experimental and clinical pharmacokinetics, Epitheorese Klin. Farmakol. Farmakokinet. 4(2): 67-86 (1990) | |
| Publication Date | Received for publication: October 20, 1989
Accepted for publication: January 29, 1990 |
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| Full Text Language | English | |
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| Keywords | Biological clocks, melatonin, chronopharmacokinetics, chronoabsorption, chronodistribution, drug-protein binding, chronoexcretion, chronotherapy, gastric acid secretion, gastric emptying, small intestine motility, membrane permeability, blood flow, antiasthmatic drugs, psychotropic drugs, anticancer drugs, nonsteroid antiinflammatory drugs, beta-adrenoceptor blocking drugs, anesthetic drugs, carbamazepine, alcohol, nifedipine, prednisolone. | |
| Other Terms | review article | |
| Summary | It has long been recognised that there are temporal variations (ultradian, circadian, infradian, circannual) in the functions of plants, animals and man. This rhythmicity is based on the chronobiologic concept close related to the biologic clocks. It appears that these clocks are located in pineal gland and are associated with melatonin biosynthesis and function. Recent investigations have shown temporal variations in the pharmacokinetic processes (i.e. absorption, distribution, metabolism and excretion) and parameters (Cmax, Tmax, AUC, t1/2). The chronoabsorption dependts on temporal variations in gastric acid secretion, gastric emptying, small intestine motility and gastric blood flow. Circadian variations in drug absorption and plasma concentration are now well established for a number of drugs, such as antiasthmatic drugs (theophylline, terbutaline), prednisolone, psychotropic drugs (diazepam, lorazepam, triazolam, amitriptyline, haloperidol, lithium), anti- cancer drugs (methotrexate, methyfprednisolone, cis-dichlorodiammine platinum, oxaliplatin, doxorubicin), beta-adrenoreceptor blocking agents (propranolol, metoprolol, sotalol, atenolol), nifedipine, isosorbide-5-mononitrat, non-steroidal antiinflammatory drugs (aspirin, indo- methacin, ketoprofen, sulindac), anesthetic drugs (lidocaine, bupivacaine, mepivacaine), alcohol and carbamazepine. In addition, the binding of drugs to plasma proteins or erythrocytes depends on the administration time, due to temporal changes occuring in membrane permeability. Temporal variations in the binding to plasma proteins have been reported for a limited number of drugs such as carbamazepine, disopyramide, licoaine, propranolol, phenytoin, diazepam and valproic acid. Temporal variations in the binding to erythrocyte have been shown for some drugs such as lidocaine, bupivacaine, mepivacaine and indomethacin. In vitro and in vivo studies have reported temporal variations in the mixed-function oxidase system in the liver resulting in temporal changes in the metabolism of some drugs and other xenobiotic substances such as aminopyrine, aniline, benzphetamine, benzpyrene, biphenyl, hexobarbital, imipramine, p-nitroanisole, ethylmorphine, phenylbutazone, antipyrine, phenacetin, sulindac and steroids. Temporal variations have also been reported in the glucuronidation, sulfate conjugation and glutathione conjugation of some drugs, as well as in the activities of several enzymes involved in renal metabolic functions. The drug chronometabolism may be influenced by the blood flow to the liver, the corticosteroid secretion and by environmental factors such as the lighting conditions. On the other hand, drug renal chronoelimination depends on temporal variations in glomerulal filtration rate, renal blood flow and urinary pH and in tubular fluid flow rate. | |
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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