Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine.

Aims: To determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics of the calcium antagonist amlodipine.

Method: S The effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral and intravenous amlodipine were assessed in 20 healthy men in a placebo-controlled, open, randomized, four-way crossover study using single doses of amlodipine 10 mg. For 9 days beginning with the day of administration of amlodipine, grapefruit juice (or water control) was given once daily, and blood samples, blood pressure and heart rate measures were obtained.

Concentrations of trovafloxacin in colonic tissue and peritoneal fluid after intravenous infusion of the prodrug alatrofloxacin in patients undergoing colorectal surgery.

Background: Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective colorectal surgery. Alatrofloxacin is a prodrug that is rapidly hydrolyzed to trovafloxacin in the body.

Methods: Twelve patients received a single dose of alatrofloxacin equivalent to 200 mg trovafloxacin by intravenous infusion over 1 hour.

Single- and multiple-dose administration, dosing regimens, and pharmacokinetics of trovafloxacin and alatrofloxacin in humans.

A simplified dosing algorithm for trovafloxacin was evaluated following a single-dose infusion of alatrofloxacin at trovafloxacin equivalent doses of 30, 100, 200, 300 and 400 mg (57 subjects), and multiple doses of 200, 300 and 400 mg (30 subjects). Maximum serum concentration and area under the concentration-time curve for trovafloxacin increased with dose. Trovafloxacin clearance (82-85 ml x h/kg) and volume of distribution (1.

Hepatobiliary elimination of trovafloxacin and metabolites following single oral doses in healthy volunteers.

Trovafloxacin, a fluoronaphthyridone derivative related to fluoroquinolones, has significant activity against gram-negative and gram-positive pathogens, including penicillin-resistant Streptococcus pneumoniae, anaerobes and atypical organisms, good tissue penetration and a long elimination half-life. Following oral administration, less than 10% of the dose is renally eliminated as unchanged drug. Hepatobiliary elimination of trovafloxacin was examined by comparing the time course and bile and serum concentrations of trovafloxacin and its metabolites following oral administration to three patients with in-dwelling nasobiliary catheters or T-tubes.