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Effect of l ‐phenylalanine supplementation and a high‐protein diet on pharmacokinetics of cefdinir in healthy volunteers: an exploratory study
Author(s) -
Fujita T.,
Nakamura K.,
Yamazaki A.,
Ozaki M.,
Sahashi K.,
Shichijo K.,
Nomura K.,
Maeda M.,
Nakamura T.,
Fujita T.,
Yokota S.,
Kuroyama S.,
Kumagai Y.,
Majima M.,
Ohtani Y.
Publication year - 2007
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2007.00826.x
Subject(s) - cefdinir , pharmacokinetics , phenylalanine , medicine , pharmacology , exploratory research , chemistry , antibiotics , biochemistry , amino acid , cephalosporin , sociology , anthropology
Summary Background: Upregulation of oligopeptide transport activity by dietary protein, certain dipeptides and amino acids has been reported in the rat intestine and a human intestinal cell line. Objective: In this study, the pharmacokinetics of cefdinir were investigated after l ‐phenylalanine supplementation and a high‐protein diet (HPD) in humans to explore changes in the activities of intestinal and renal oligopeptide transporters. Methods: A normal‐protein diet (NPD, 73·2 ± 2·6 g/day), NPD + l ‐phenylalanine (7·5 g/day), or HPD (141·3 ± 3·7 g/day) was given to six male healthy volunteers for 12 days followed by a single dose of cefdinir after an overnight fast in a randomized three‐way crossover study with a 22‐day washout. Blood and urine were collected over a 12‐h period after administration of cefdinir. Concentrations of cefdinir in plasma and/or urine were measured by high‐performance liquid chromatography. Results: Plasma concentrations and urinary excretion of the drug did not change throughout the study. Physiological variables and laboratory values did not reveal any differences between the three periods except for serum and urinary nitrogen levels and serum triglyceride. Discussion: A reason for the unchanged pharmacokinetics of cefdinir may be due to lower doses of l ‐phenylalanine and protein in humans than in animals when converting animal effective doses to humans. Conclusion: In humans, l ‐phenylalanine supplementation and HPD do not seem to upregulate intestinal and renal oligopeptide transport in the ranges of duration and dose examined.