Relative bioavailability of four clomipramine hydrochloride tablet products.

The relative bioavailability of clomipramine was determined in two single-blind, single-dose, randomized, crossover studies. In the first study, the relative bioavailability of the test product, 2 x 25 mg clomipramine hydrochloride tablets (Noristan Ltd.), with respect to the reference product, Anafranil 2 x 25 mg tablets (clomipramine HCl; Ciba-Geigy (Pty) Ltd.) was determined. In the second study, the relative bioavailability of the test product, 5 x 10 mg clomipramine hydrochloride tablets (Noristan Ltd.), with respect to the reference product, Anafranil 5 x 10 mg tablets (clomipramine HCl; Ciba-Geigy (Pty) Ltd.), was determined. The geometric mean values for the variable Cmax were 31.3 ng mL-1 for the reference and 31.6 ng mL-1 for the test product in study 1. The geometric mean values for the variable AUC were 736 ng h mL-1 and 753 ng h mL-1 for the reference and test, respectively. In study 2, the geometric mean Cmax values were 25.8 ng mL-1 and 23.9 ng mL-1 for the reference and test respectively; the geometric mean AUC values were 569 ng h mL-1 and 547 ng h mL-1. The 90% confidence intervals for the 'test/reference' mean ratios of the plasma clomipramine pharmacokinetic variables Cmax and AUC(0-infinity) (as measures of the rate and extent of absorption of clomipramine, respectively) fall within the conventional bioequivalence range of 80-125% for both studies. The test products (clomipramine HCl) are therefore bioequivalent to the reference products (Anafranil) with respect to the rate and the extent of absorption of clomipramine in both 10 mg and 25 mg strengths.

Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers.

Fifteen healthy male volunteers participated in an open, multiple-dose study to investigate a possible interaction between furosemide and meloxicam, a new non-steroidal anti-inflammatory agent (NSAID). The study comprised three treatment periods. First, furosemide (40 mg) was administered as a single oral daily dose for 3 days. A wash-out day was followed by the administration of meloxicam (15 mg) as a single oral daily dose for 10 days. Thereafter, meloxicam and furosemide were administered concomitantly at the same doses as described above, for 3 days. The effect of concomitant ingestion of meloxicam and furosemide on furosemide-induced diuresis, urine and serum electrolytes, and furosemide pharmacokinetics was determined, after both single and repeated administration of furosemide. Estimates of the "(furosemide+meloxicam)/(furosemide alone)" mean ratio of the variable AUC(0-infinity) for plasma furosemide and the cumulative sodium excretion (0-8 h) were 97.4% (90% confidence interval 89.7-106%) and 88% (90% confidence interval 82-94%), respectively. The study results indicate that meloxicam does not affect the pharmacokinetics of furosemide in healthy volunteers, nor does it affect furosemide-induced diuresis or serum electrolytes. The cumulative urinary electrolyte excretion after concomitant administration of meloxicam and furosemide is somewhat lower than after administration of furosemide alone, in particular for the period 0-8 h after administration of furosemide. This effect of meloxicam on furosemide dynamics is small, and is probably not clinically relevant in healthy volunteers under the dosing regime studied.