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

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 13 th 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, C max , T max , AUC last 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