Phase I pilot study of the effects of trovafloxacin (CP-99,219) on the pharmacokinetics of theophylline in healthy men.
This study examined the effect of trovafloxacin (CP-99,219) on the pharmacokinetics and pharmacodynamics of a single dose of theophylline, when administered to steady-state concentrations. Twelve healthy, nonsmoking male volunteers participated. A 450-mg dose of theophylline was administered at 7:00 AM on day 1. On day 4, volunteers received 300 mg of trovafloxacin (CP-99,219) daily in the morning for 7 days. The 450-mg dose of theophylline was repeated on day 8 at 7:00 AM concomitantly with 300 mg of trovafloxacin. Theophylline concentrations in plasma and trovafloxacin in serum were determined using reverse-phase high-performance liquid chromatography. There was no significant difference between the geometric mean values for Cmax of theophylline, 6.42 micrograms/mL and 6.00 micrograms mL on days 1 and 8, respectively. A change (P = 0.032) in the geometric mean of the area under the concentration-time curve extrapolated to infinity (AUC0-infinity) for theophylline was noted for trovafloxacin was administered. Mean terminal phase elimination rate constants (Kes) were reduced (P = 0.001) by 13% after administration of trovafloxacin from day 1 to day 8. In general, changes in theophylline clearance of less than 20% are unlikely to be of clinical significance. In this study, oral administration of trovafloxacin in 300 mg doses to achieve steady-state concentration resulted in an 8.4% increase in the extent of systemic exposure (AUC0-infinity) to theophylline. Assuming that this AUC change is based on oral clearance and not absorption, one would not expect to see clinically significant changes in the pharmacokinetics of theophylline. No pharmacodynamic changes resulted from the pharmacokinetic changes of theophylline.
Dickens
G R
GR
Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, USA.
Wermeling
D
D
Vincent
J
J
D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D010865:Pilot Projects; D013806:Theophylline / Q000009:adverse effects / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D001993:Bronchodilator Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin; D013806:Theophylline