Pharmacokinetic behavior in sheep and cattle of 5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazole, a new fasciolicide agent.

The physicochemical properties, pK(a), Log P and solubility of compound alpha, (5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazole), a new fasciolicide agent, were characterized using conventional methods. Also, its pharmacokinetics was evaluated in sheep and cattle. In both species an oral dose of 12 mg/kg was administered. Blood samples were collected during 144 h and analyzed by using an HPLC assay. Results showed that compound alpha is a weak base with a pK(a) value of 2.87 and log P of 1.44. The solubility was very low in aqueous solvents. Pharmacokinetic studies showed that in both species compound alpha could not be detected at any sampling time. The mean half-life (t(1/2)) values of alpha sulphoxide in sheep and cattle were 19.86 and 29.87 h, while the half-life values of alpha sulphone were 19.43 and 46.32 h respectively. C(max) values of alpha sulphoxide did not differ between species while alpha sulphone values were higher in cattle. Plasma protein binding of alpha sulphoxide was between 82% and 86%. These results, combined with the previous efficacy studies, suggest that compound alpha could be a promising fasciolicide agent.

Pharmacokinetics of a sustained-release dosage form of clomipramine.

In this study, the pharmacokinetic parameters of the sustained-release (SR) dosage form of clomipramine (CMI) were compared with those obtained after the administration of the immediate-release (IR) dosage form. Two studies were performed. In the first study, a single oral dose of both products was administered in 12 healthy volunteers, and in the second study, multiple doses of both products were administered in 6 patients with depression in which steady-state plasma levels (Css) were determined. Plasma levels were assayed using an HPLC method. In the single-dose study, the mean Cmax and AUC values of CMI were 63.37 ng/mL-1 and 1375.38 ng.h/mL-1 for the reference product and 32.55 ng/mL-1 and 1285.26 ng.h/mL-1 for the test product, respectively. The mean beta and MRT values of CMI were 0.030 h-1 and 47.21 h for the reference product and 0.026 h-1 and 55.63 h for test product, respectively. Results showed that after the multiple-dose study, the mean clomipramine plus demethylclomipramine values of Cavss were 406.2 ng/mL-1 for the reference and 328.6 ng/mL-1 for the sustained-release dosage form. This product also presented less fluctuation in steady-state plasma levels (1.08 vs. 1.23). The values of MRT and tmax were higher for the SR dosage form, showing that the drug was maintained longer in the body. The mean values for the ratio metabolite/drug were 2.06 and 2.41 for the IR and SR dosage forms, respectively. Neither AUC nor elimination half-life was affected significantly after the administration of the sustained-release dosage form.

The distribution of 10-hydroxy carbazepine in blood compartments.

The distribution of 10-hydroxy carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), was investigated in plasma and red cells. After the oral administration of 600mg of OXC to nine healthy volunteers, blood samples were withdrawn for the next 56h and packed red cells were separated from plasma by centrifugation. Also, in vitro studies of plasma binding of MHD were carried out by a dialysis technique. Results showed that the in vitro protein binding was low. The mean bound concentration ranged from 37 to 40%; however, an affinity of MHD to red corpuscles was found. These observations indicate that MHD red blood cell concentrations together with plasma measurements could be useful in cases of inefficacy or toxicity in order to make the appropriate drug adjustments.