Bioavailability Study of Drotaverine from Capsule and Tablet Preparations in Healthy Volunteers

Abstract

The bioavailability of drotaverine (CAS 14009-24-6) was investigated after oral administration of a drotaverine capsule preparation (20 mg Droxa mite) and compared to that of a reference tablet preparation. The preparations were investigated in 23 healthy volunteers, aged between 20 and 27 years, according to a randomised two-way, cross-over design in the fasted state. Blood samples for determination of drotaverine plasma concentrations were collected at pre-defined time points up to 30 h following drug administration. A washout period of two weeks separated both treatment periods. Drotaverine plasma concentrations were determined by means of a validated HPLC method (UV detector, imipramine HCl salt as an internal standard). The limit of detection was 6 ng/ml. Values of 1593.92 +/- 949.70 ng x h/l (95% confidence interval (CI): 1183.20-2004.60) for the test and 1705.48 +/- 737.78 ng x h/l (95% CI: 1386.40-2024.50) for the reference preparation AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum concentrations--Cmax of 121.89 +/- 37.03 ng/ml (95% CI: 104.05-139.80) and 121.85 +/- 37.97 ng/ml (95% CI: 107.09-135.74) and time to reach maximum plasma concentration--Tmax of 1.29 +/- 0.42 h (95% CI: 1.11-1.48) and 1.14 +/- 0.34 h (95% CI: 0.99-1.29) achieved for the test and reference preparations did not differ significantly. The relative bioavailability (AUC(0-infinity) ratio test/reference) and Cmax ratio test/reference were 103.15% (90% CI: 81.68-124.60) and 103.74% (90% CI: 94.10-113.38), respectively. AUC was calculated using two different methods. There were no significant differences between the obtained values. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the European Agency for the Evalution of Medicinal Products (CPMP) and the Food and Drug Administration, it is concluded that the new drotaverine capsule formulation is therapeutically equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.

The Influence of Oral Drotaverine Administration on Materno–Fetal Circulation during the Second and Third Trimester of Pregnancy

“…Nevertheless, in O Balii's et al research, it was pointed out that the high variation in the bioavailability of drotaverine HCl after oral administration may result in significant interindividual differences in terms of therapeutic response [14]. We chose the 90-120 min interval after the oral administration of drotaverine in order to perform our measurements at the point when the drug was at its highest potential concentration [16].…”

The Effect of Drotaverine on Gastrointestinal Motility and Heart Rate Variability in Normal, Resting Horses

“…In humans, drotaverine can suppress spasm-associated pain and is successfully used in the symptomatic treatment of various conditions such as gastrointestinal, urinary, biliary, vasomotor diseases associated with smooth muscle spasms [1,11], it has a cytostatic effect [12] and improves cognitive function [13]. It is available without prescription in many countries of Central and Eastern Europe (Poland [11,[14][15][16], Hungary [17], Estonia, Croatia, Latvia [4], Romania [18,19]), Africa (Nigeria [20]) and Asia (India [21][22][23], Russia [24], China [25] under several brand names.…”

The Influence of the Intergranular Superdisintegrant Performance on New Drotaverine Orodispersible Tablet Formulations

“…It is used for alleviating pain associated with irritable bowel syndrome, biliary colics, and renal colics, along with gynecological conditions such as dysmenorrhea [ 22 ]. Considering that it does not cross the placental barrier, DROT-HCl is used with great results in the dilatation stage of labor for shortening its length [ 18 ]. Furthermore, an enormous benefit is found in the lack of anticholinergic side effects and the infrequent adverse reactions [ 21 ].…”

“…Regarding distribution, the selected API is known for its strong binding to plasma proteins (95-98%), notably to albumin, but to beta and gamma globulins as well. DROT-HCl is rapidly metabolized at hepatic level by O-deethylation [18], and it is excreted through urine and feces as highlighted in human studies [19]. In a study conducted on rats, it has been shown that the active ingredient can be eliminated into the bile-producing conjugated metabolites, among which 4 desethyl-drotaveraldine is predominant [20].…”