Pharmacokinetics of d(+)-usnic acid in rabbits after intravenous administration.

The pharmacokinetics of usnic acid, a lichen antitubercular, antitumor and enzyme inhibiting agent, was studied in normal male rabbits after administration of 5 mg/kg dose by intravenous route. Plasma samples were collected up to 48 h. The plasma usnic acid levels showed a triexponential decay with a terminal half life of 10.69 h. The mean volume of distribution of the central compartment was 43.93 ml/kg. The pharmacokinetic parameters obtained from a three-compartment body model and a noncompartment body model gave close values. The mean steady-state volume of distribution was 167.17 and 163.29 ml/kg, systemic clearance was 12.17 and 12.25 ml/h/kg and AUC was 428.51 and 426.69 micrograms.ml/h following three-compartmental and noncompartmental analyses respectively.

Pharmacokinetics of D(+)-usnic acid in rabbits after intravenous and oral administration.

The pharmacokinetics of D(+)-usnic acid--a lichen antitubercular, antitumor, and enzyme-inhibiting agent--was studied in rabbits following intravenous or oral administration of 5 and 20 mg/kg body weight doses, respectively. Plasma samples were collected at different time intervals, and usnic acid was determined by HPLC. Plasma usnic acid levels following intravenous administration showed a triexponential elimination with a mean +/- SD terminal half-life of 10.7 +/- 4.6 hr. The volume of distribution of the central compartment and systemic clearance were 43.9 +/- 21.3 ml/kg and 12.2 +/- 3.0 ml/hr/kg, respectively. Pharmacokinetic parameters obtained, based on compartmental and noncompartmental approaches, were comparable. Plasma concentration data obtained after oral administration were analyzed using a noncompartmental method. Peak plasma level (Cmax) of 32.5 +/- 6.8 micrograms/ml was achieved in 12.2 +/- 3.8 hr (tmax). Mean absolute bioavailability of usnic acid following oral administration was 77.8%.

Role of rifampin and clofazimine ointments in the treatment of leprosy.

The use of rifampin and clofazimine ointments alone and in combination over the patches of tuberculoid patients had a beneficial effect. In combination (rifampin and clofazimine), erythema, inflammation, and edema are considerably reduced. For some of the cases with a recent appearance of a patch, the patch completely disappeared. It is suggested that topical therapy with rifampin and clofazimine ointments would be economical and beneficial in tuberculoid leprosy.

High-performance liquid chromatographic determination of usnic acid in plasma.

A high-performance liquid chromatographic method for the determination of usnic acid in human plasma using diclofenac sodium as internal standard is described. Plasma proteins were precipitated with methanol. A 250 mm x 4 mm I.D. Nucleosil. C18 (5 microns) column with a mobile phase consisting of methanol-phosphate buffer (pH 7.4) (70:30, v/v) was used. Chromatography was performed at ambient temperature with flow-rate of 1 ml min-1 and ultraviolet detection at 280 nm. Each analysis required no longer than 7 min. Quantification was achieved by measurement of the peak-height ratio and the absolute recovery varied from 93.8 to 97.3%. The limit of quantitation of usnic acid in plasma was 0.25 micrograms ml-1. The intra-day relative standard deviation (R.S.D.) ranged from 1.24 to 4.53% and the inter-day R.S.D. from 2.23 to 8.25% at three different concentrations. The method was applied to the determination of plasma levels of usnic acid after intravenous and oral administration to study its disposition in a healthy male rabbit.