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.
Müller
F O
FO
Department of Pharmacology, University of the Orange Free State, Bloemfontein, Republic of South Africa.
Schall
R
R
Mogilnicka
E M
EM
Groenewoud
G
G
Hundt
H K
HK
Luus
H G
HG
Middle
M V
MV
Swart
K J
KJ
De Vaal
A C
AC
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002997:Clomipramine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D016037:Single-Blind Method; D013607:Tablets
D000929:Antidepressive Agents, Tricyclic; D013607:Tablets; D002997:Clomipramine