Chronopharmacokinetics of Sumatriptan in Healthy Human Subjects

Abstract

Rhythms in the onset and symptoms of several diseases are well established. Migraine is a disorder that exhibits periodicity in its symptoms and so chronotherapy may be beneficial in treating the problem. Designing a chronotherapeutic schedule requires chronopharmacokinetic and chronopharmacodynamic data of the drugs prescribed. We have studied the chronopharmacokinetics of sumatriptan, a drug of choice in migraine treatment. Twelve healthy male volunteers were treated with 100 mg sumatriptan orally at 0700, 1300, 1900 and 0100 h in a randomized 4 x 4 Latin square crossover design, with a wash-out period of one week. Serum samples were analysed by high performance liquid chromatography with an electrochemical detector. Pharmacokinetic parameters were calculated using noncompartmental methods. The pharmacokinetic parameters were analysed using analysis of variance and a two-tailed paired t-test at the probability of 95%. The mean peak serum concentration following the 0700 h administration (Cmax; 59.09 +/- 10.53 ng mL(-1)) was significantly (P < 0.05; n = 12) higher than after the 1900 h administration (Cmax 41.88 +/- 12.21 ngmL(-1)). The mean area under the serum concentration-time curve from time zero to the last time-point (AUCo-t), the area under the serum concentration-time curve from zero to infinity (AUC 0-infinity), and the area under the first moment curve (AUMC) were significantly (P < 0.05; n = 12) higher following the 0700 and 0100 h administrations than after the 1900 h administration. Following administration at 0700 h, the mean oral clearance (CLs/f; 781 +/- 186 mL h(- 1) kg(-1)) and the apparent volume of distribution (Vd/f; 2,379 +/- 684) were significantly lower (P < 0.05; n = 12) than after the 1900 h administration (CLs/f 1,208 +/- 458 mL h(-1) kg(-1), Vd/f 4,655 +/- 2,096 mL kg(-1)). The mean Vd/f value was again lower after the 1300h administration than after the 1900 h administration (2,763 +/- 1,417 vs 4,655 +/- 2,096 mL kg(-1); P < 0.05; n = 12). The variations may be due to the time dependent changes in the extent of absorption and/or circadian variations in hepatic blood flow.

Pharmacokinetic Behaviors of Orally Administered Drugs

“…13.26). It was also observed that AUC was significantly higher following administration at 07:00 h than that at 19:00 h, while the oral clearance and volume of distribution were significantly lower after administration in the morning (07:00 h) (Poondru et al, 2000).…”

Appropriateness of timing of drug administration in electronic prescriptions

“…certain pharmacokinetic parameters as in the case of sumatriptan [51]), or other factors which are less essential for patient care. As a general rule this algorithm therefore preferred trials with clinical endpoints over pharmacokinetic studies or studies involving healthy volunteers.…”

Chronopharmacokinetic and Metabolite Studies of the Cardiovascular Medication Sacubitril

“…The primary objective of the research was to examine the drug's enantioselective behavior following administration. [17][18][19] • Dosing and plasma sample collection After heating the vein with hot water, a 1-mL syringe containing 1.6 mg/kg of Sacubitril solution was inserted into the caudal vein of the rat and filled. Three animals were employed at each of the following times after drug administration: 4, 8, 16, 32, 46, 1, 2, 4, and 8 hours.…”