Pharmacokinetics of cefdinir in healthy subjects after high protein diet and l-phenylalanine load

Abstract

Aims To explore induction of intestinal peptide transporter (PEPT) by protein and amino acid load in human. Methods Six healthy subjects had normal (NP, 1.1±0.1g/kg/day) and high (HP, 2.1±0.2g/kg/day) protein diets, a permissible upper limit intake, and L-phenylalanine (Phe, 7.5 g/day) for 12 days in a randomized 3-way crossover study. A single dose of cefdinir (100 mg), a substrate for PEPT, was given on the 13th day. Serial plasma samples were collected and measured by HPLC. Results Urinary urea nitrogen levels were increased by HP (5.9±0.5 g/12h (Mean±SD) vs 4.1±0.3 g/12h:NP, p<0.01). Plasma trough Phe levels were increased to 121±13.5% of the basal levels by Phe (p<0.01). However, Cmax, Tmax, AUClast in the HP (802.0±264.3 ng/mL, 3.5±0.5 h, 3347.9±1366.6 ng h/mL) and Phe (878.7±276.0 ng/mL, 3.3±0.8 h, 3549.9±1358.2 ng h/mL) groups were not different from the NP group (839.2±368.2 ng/mL, 3.5±0.8 h, 3628.2±1668.9 ng h/mL). Conclusions Intestinal PEPT did not seem to be affected by high protein diet and Phe load within the subjects, duration and doses examined. A further study is planned to confirm induction of PEPT in human. Clinical Pharmacology & Therapeutics (2005) 77, P81–P81; doi: 10.1016/j.clpt.2004.12.203