The effect of pregnancy on hepatic drug-metabolizing enzyme activity was investigated in nine healthy pregnant women using the ratio of 6-hydroxycortisol (6-OHF), to total 17-hydroxycorticosteroid (17-OHCS) in 24-hour urine as an index of the hepatic monooxygenase activity. The values of 6-OHF and the ratio (713 +/- 250 micrograms/d and 0.323 +/- 0.242; mean +/- SD) before delivery were significantly higher than they were during early puerperium (395 +/- 145 micrograms/d and 0.114 +/- 0.055) and approximately three months after delivery (237 +/- 67 micrograms/d and 0.066 +/- 0.034). Although the values three months after delivery were comparable to those found in the nonpregnant group (n = 10; 228 +/- 48 micrograms/d and 0.081 +/- 0.031), 6-OHF values one week after delivery were significantly higher than those observed in the control group. These observations suggest that drug-metabolizing enzyme induction may occur during pregnancy.

The effect of three new fluoroquinolones on theophylline kinetics and the urinary excretion of metabolites was studied in 5 healthy subjects (3 male, 2 female). All subjects received serial, single i.v. infusions of theophylline (aminophylline, 250 mg) over 60 min after 200 mg doses of a quinolone (enoxacin, ofloxacin, norfloxacin) every 8 h for 3 consecutive days, the quinolone being administered up to the day following theophylline administration. Pretreatment with ofloxacin and norfloxacin did not influence theophylline disposition, but theophylline clearance fell from 0.054 to 0.027 l.h-1.kg-1 in the presence of enoxacin, without a change in the apparent volume of distribution. Enoxacin, too, was the sole compound to increase the urinary excretion of theophylline (33.2 vs 43.9 mg, before vs after treatment), and significantly to decrease the excretion of 3-methylxanthine (3-MX), 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU) in 24-h urine samples (from 19.8 to 7.16 mg, from 28.3 to 10.3 mg and from 68.8 to 49.5 mg, respectively). The effect of the quinolones on hepatic drug metabolizing enzyme activity was investigated in each subject using the ratios of 6-hydroxycortisol to total 17-hydroxycorticosteroids and to free cortisol in 24-h urines as an index of the hepatic P-450-dependent enzyme system. No significant difference in ratio was observed between control and other treatments. It is concluded that the theophylline-enoxacin interaction was largely due to inhibition of a metabolic system other than the common hepatic P-450 system.