PRAZIQUANTEL Tablets Ref.[8692] Active ingredients:

Absorption and bioavailability

After oral administration praziquantel is rapidly absorbed. It undergoes first-pass metabolism and 80% of the dose is excreted mainly as metabolites in the urine within 24 hours.

Following single dose administration of 2 tablets Praziquantel 600mg Tablets in two sequences (full replicate design), used to compare the bioavailability of this product with the same dose of the reference formulation, mean C_max (± SD) values of praziquantel were 1363 ng/ml (±880) at T1 and 1372 ng/ml (±962) at T2 and the corresponding AUC values were 2938 ng.h/ml (±1607) at T1 and 3098 ng.h/ml (±1936) at T2. The mean (± SD) tmax values were 2.44 (±1.74) hours and 2.55 (±1.36) hours at T1 and T2, respectively.

Distribution

Praziquantel is 80% bound to serum proteins. It passes the blood-brain barrier and liquor concentration is about 14–20% of the concurrent total (free plus protein-bound) plasma concentration. Praziquantel is excreted in the milk of nursing mothers in concentrations about 25% of maternal serum concentrations.

Biotransformation

Praziquantel is subject to first pass effect and extensive metabolism in the liver, mainly via the cytochrome P450 isoenzymes CYP2B1 and CYP3A4. One hour after administration only approximately 6% of the medicine in serum is in the unmetabolised form.

Elimination

Approximately 80% of a dose of praziquantel is excreted in the kidneys within four days, almost exclusively (>99%) in the form of metabolites. Excretion might be delayed in patients with impaired renal function, but accumulation of unchanged drug would not be expected.

Pharmacokinetics in hepatic impairment

The pharmacokinetics of praziquantel were studied in 40 patients with Schistosoma mansoni infections with varying degrees of hepatic dysfunction. In patients with schistosomiasis, the pharmacokinetic parameters did not differ significantly between those with normal hepatic function (Group 1) and those with mild (Child-Pugh B) hepatic impairment. However, in patients with moderate-to-severe hepatic dysfunction (Child-Pugh Class B and C), praziquantel half-life, C_max, and AUC increased progressively with the degree of hepatic impairment. In Child-Pugh class B, the increases in mean half-life, C_max, and AUC relative to Group 1 were 1.58-fold, 1.76-fold, and 3.55-fold, respectively. The corresponding increases in Child-Pugh class C patients were 2.82-fold, 4.29-fold, and 15-fold for half-life, C_max, and AUC.

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the human exposure indicating little relevance to clinical use.

Carcinogenesis

Mutagenic effects in Salmonella tests found by one laboratory have not been confirmed in the same tested strain by other laboratories. Long term carcinogenicity studies in rats and golden hamsters did not reveal any carcinogenic effect.

Reproductive toxicity

Reproduction studies have been performed in rats and rabbits at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the foetus due to praziquantel. An increase of the abortion rate was found in rats at three times the single human therapeutic dose.