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Dietary patterns and diurnal variations in aminopyrine disposition
Author(s) -
Shively Carol A,
Simons Richard J,
Passananti G Thomas,
Dvorchik Barry H,
Vesell Elliot S
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.12
Subject(s) - diurnal temperature variation , chemistry , bioavailability , circadian rhythm , medicine , meal , endocrinology , pharmacokinetics , volume of distribution , saliva , zoology , pharmacology , biology , biochemistry , atmospheric sciences , geology
In healthy, nonmedicated male subjects, patterns of eating and fasting determined diurnal variations in aminopyrine disposition. Under dietary conditions used in our laboratory to study temporal variation in the disposition of aminopyrine (a 12‐hr fast preceding 8 A.M. dose and a 5 P.M. meal before 8 P.M. drug dosing) there was a mean diurnal variation of 33% in saliva aminopyrine half‐life (t½) and of 46% in apparent volume of distribution (aVd) with shorter t½ and lower aVd at 8 A.M. Mean metabolic clearance rate (Cl) was unchanged. Fasting for 32 and 44 hr before aminopyrine at 8 A.M. and 8 P.M. ablated this temporal variation in aminopyrine t½ and aVd. Reversal of eating times (a 12‐hr fast before the 8 P.M. aminopyrine dose and a 5 A.M. meal before the 8 A.M. dose) reversed the direction of the diurnal variation of aminopyrine t½ and aVd so that aminopyrine t½ and aVd were larger at 8 A.M. but fasting for 32 or 44 hr did not alter the normal circadian rhythms of plasma 11‐hydroxycorticoids identified in our subjects at 8 A.M. and 8 P.M. Plasma protein binding of aminopyrine, determined at 8 A.M. after a 12‐hr fast (29.8%), was higher than at 8 P.M. (23.3%, p < 0.05). Aminopyrine protein binding rose to 38.1% and 32.9% after a fast of 32 and 44 hr. Mean bioavailability and area under the curve of aminopyrine determined in plasma at 8 A.M. and 8 P.M. showed no diurnal change. As in saliva, aminopyrine concentrations in plasma revealed that mean aminopyrine t½ was 34% longer, mean aminopyrine aVd 33% larger, but mean aminopyrine Cl the same at 8 P.M. as at 8 A.M. These results suggest that meals decrease protein binding of aminopyrine, leading to increased aminopyrine aVd and t½, possibly due to increased tissue uptake of aminopyrine. Aminopyrine plasma concentrations after oral doses of 2, 4, and 8 mg/kg at 1‐wk intervals to each of six normal male subjects revealed dose dependence of aminopyrine t½ and hepatic first‐pass effect. Clinical Pharmacology and Therapeutics (1981) 29, 65–73; doi: 10.1038/clpt.1981.12