4-quinolones inhibit biotransformation of caffeine

Abstract

The pharmacokinetics of caffeine, including formation of its major metabolite paraxanthine in plasma, has been investigated in 12 healthy males (age 20-40 years) alone and during co-administration of the 4-quinolones ofloxacin, norfloxacin, pipemidic acid, ciprofloxacin, and enoxacin; ciprofloxacin and enoxacin were given in 3 different dose levels. The naphthyridine derivative enoxacin and the pyrido-pyrimidine derivative pipemidic acid had caused marked inhibition of caffeine and paraxanthine metabolism, whereas the genuine quinolone derivatives norfloxacin and ciprofloxacin had little effect, and the pyrido-benzoxacine derivative ofloxacin had no detectable effect. The different molecular and spatial structures of the compounds appear to be responsible for the differences in inhibitory potency.

Quinolones: a class of antimicrobial agents

“…After repeated administration the fluoroquinolones, including enrofloxacin, have been shown to decrease the hepatic clearance and to increase the elimination halflife of theophylline (Rybak et al, 1987;Bowles et al, 1988) and caffeine (Harder et al, 1988) reportedly by decreasing the demethylation of theophylline by the hepatic P450 enzymes, the 4-oxoquinolone metabolite. Ciprofloxacin administration over a period of 8-10 days prolonged the half-life of antipyrine from 9.45 to 14.9 h attributed to decreased clearance from 0.85 to 0.52 ml/min/ kg in human patients (Ludwig et al, 1988).…”

Testing Low Doses of Caffeine on Respiratory Resistance Using the Airflow Perturbation Device

“…Previous caffeine studies have been conducted at a wide variety of dosages, ranging from 3 [14] to 13 [8] mg/kg. Some studies chose to use a specific mass of caffeine rather than a dosage per body weight [9], [11], and [15]. 3 -4.5 mg/kg was selected for this experiment because it is at the lower, and therefore safer, end of this range.…”

“…Weekly Exerciser (hr) 6.4 ± 3.7 (14) 5.0 ± 4.0 (12) 6.1 ± 3.8 (15) APD to maintain proper hygiene. Subjects were also given disposable nose clips, which prohibited air from escaping through the subjects' noses, forcing all inhalation and exhalation flow through the mouth, and therefore through the APD.…”

Lack of interaction between lomefloxacin and caffeine in normal volunteers

“…The frequencies of central nervous system-related effects for the two treatments were not statistically different. We conclude that lomefloxacin has no significant effect on the disposition of caffeine in young healthy volunteers.Several quinolone antibiotics, including enoxacin, ciprofloxacin, and pefloxacin, have been reported to interfere with the clearance of methylxanthine compounds such as theophylline and caffeine, leading to elevated concentrations of the xanthine in serum (1,9,10,17,19,23,29,33,34) and, in the case of theophylline, central nervous system (CNS) toxicity (13,20,30,32). However, other quinolones such as norfloxacin, ofloxacin, and fleroxacin appear to have minimal or no effect on methylxanthine disposition (3,5,6,9,11,16,21,25,34).…”

“…However, other quinolones such as norfloxacin, ofloxacin, and fleroxacin appear to have minimal or no effect on methylxanthine disposition (3,5,6,9,11,16,21,25,34).…”