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A simple and sensitive kinetic method for the determination of oxamniquine in pharmaceutical preparations and biological fluids was developed. The procedure is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time of 20 min. The absorbance of the colored manganate ions was measured at 610 nm. Alternatively, the decrease in the absorbance of potassium permanganate after addition of the drug was measured at 525 nm. The absorbance concentration plots in both procedures were rectilinear over the range 0.5-4 microg ml(-1). The concentration of oxamniquine is calculated using the corresponding calibration equation for the fixed-time method. The determination of oxamniquine by fixed-concentration and rate-constant methods was feasible with the calibration equations obtained but the fixed time method had been found to be more applicable. Both procedures were applied to the determination of oxamniquine in formulations. The results obtained were in good agreement with those obtained using the official method. The fixed time method of 20 min was further applied to spiked human urine and plasma, the recoveries (%) were 100.94 +/- 0.57 and 98.07 +/- 0.88 for urine and plasma, respectively, at 610 nm, and 97.51 +/- 1.27 and 95.69 +/- 1.23 for urine and plasma, respectively, at 525 nm.

A highly sensitive and specific fluorimetric method was developed for the determination of oxamniquine in biological fluids (urine and plasma). The proposed method is based on the reduction of oxamniquine using zinc/calcium chloride to obtain its nitroso derivative. The latter is then allowed to react with 2-cyanoacetamide to get a highly fluorescent product. The different experimental parameters affecting the intensity of the fluorescence were carefully studied and incorporated into the procedure. Under the described conditions, the method is applicable over the concentration range of 0.08-0.88 microgram/ml with a minimum detectability (S/N = 2) of 8 ng/ml. The percentage recoveries from spiked urine and plasma were 99.75 +/- 1.58 and 97.46 +/- 0.44%, respectively.

The pharmacokinetics of the schistosomicidal agent oxamniquine (6-hydroxmethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetra hydroquinoline) were studied in 8 (4 male, 4 female) New Zealand White rabbits and 5 female Wistar rats, following intravenous administration (15 mg/kg). The pharmacokinetic parameters (mean +/- SD) in the rabbit and rat, respectively, were as follows: plasma clearance, 65.5 +/- 33 and 17.2 +/- 5.7 ml/min/kg; steady-state volume of distribution, 7.9 +/- 4.5 and 2.1 +/- 0.5 l/kg; terminal elimination half-life, 1.8 +/- 0.3 and 1.8 +/- 0.9 h. Oxamniquine appeared to be widely distributed in both species, although significantly higher in the rabbit. Similarly, plasma clearance was significantly higher in the rabbit. Using reported estimates of liver blood flow and fractions excreted unchanged in urine of the rabbit and rat, calculations based on blood clearances indicated that oxamniquine has a low hepatic extraction ratio (0.2) in the rat and an intermediate hepatic extraction ratio (0.6) in the rabbit. From separate experiments, however, hepatic extraction appeared to be low in the rabbit, suggesting that oxamniquine disposition is probably broadly similar in both rabbit and rat.

Oxamniquine pharmacokinetics were studied following oral administration of 750, 1000 mg or 1250 mg (equivalent to approximately 15 mg/kg) to five healthy Kenyan African volunteers. Peak plasma concentrations ranging between 1 and 4.3 mg/1 were achieved 1 to 4 h after dosing. The estimated mean elimination half-life (t1/2) was 2.2 h. Despite the limited number of subjects in the study, it is concluded that the pharmacokinetics of oxamniquine in healthy Kenyan Africans do not markedly differ from those in Africans from other regions of the continent where previous studies have been reported.

Brain and plasma concentrations of oxaminiquine were determined following intravenous dosing (15 mg kg-1) in female Wistar rats. Maximum brain concentrations were achieved one hour after dosing and at all sampling times oxamniquine levels were higher in brain tissues compared to the corresponding plasma samples. It is concluded that the reported adverse neurological effects associated with the clinical use of oxaminiquine in man may be due to the passage of sufficiently large quantities of this drug into the CNS.

A method for the analysis of oxamniquine in serum (or plasma), sensitive to 10 ng/ml, was developed. Oxamniquine and a close structural analog as the internal standard were extracted from serum with ether. After derivatization with N,O-bis(trimethylsilyl)acetamide, oxamniquine was determined as its trimethylsilyl ether derivative by GLC using an electron-capture detector. The method was developed to study serum concentration profiles of different dosage forms of oxamniquine.

1. The extent of metabolism of oxamniquine, 6-hydroxymethyl-7-nitro-2-isopropylaminomethyl-1,2,3,4-tetrahydroquinoline, in the gut of the dog has been studied using an intestinal preparation which allows collection of the outflow from the portal vein. 2. Oxamniquine undergoes substantial conversion to 2-isopropylaminomethyl-7-nitro-1,2,3,4,-tetrahydroquinoline-6-carboxylic acid before or during absorption. 3. This oxidation is not significantly inhibited by pretreatment with pyrazole, erythromycin or gentamicin. 4. Results indicate that appreciable oxidation of oxamniquine is mediated via enzymes in the gut wall.