Bioequivalence testing of a new tablet formulation of generic fluoxetine.

The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

[Toxic effects of anesthetics: rhabdomyolysis with acute renal insufficiency]. / Toksicno dejstvo anestetika: rabdomioliza sa akutnom bubreznom insuficijencijom.

Rhabdomyolysis is rare but serious complication of general anesthesia. The authors report a case of anesthesia-induced severe rhabdomyoloysis in previously healthy male. First symptoms and signs occurred after the surgery was finished, and consisted of muscular pain and cardiac arrhythmia. Laboratory analysis revealed metabolic acidosis, electrolyte disturbances and marked elevation of enzyme activity, with extremely high value of creatine phosphokinase (CPK)-173920 U/I on the second day. Acute renal failure has also developed. Based on the reports of similar cases, the etiology, pathogenesis, therapy and prevention of rhabdomyolysis were discussed.

[Carbamazepine cardiotoxicity in acute poisoning]. / Kardiotoksicnost karbamazepina u akutnim trovanjima.

Manifestations of cardiotoxicity in 9 patients with acute carabamazepine poisoning treated at the Clinic of Toxicology and Clinical Pharmacology of the M.M.A. in 1989 are reported. In all patients together with symptoms and signs characteristic for acute carbamezapine poisoning, there have been also present disorders of the cardiovascular system. The most common clinical signs of cardiotoxicity have been tachycardia and hypotension, and electrocardiographic, ventricular extrasystoles and repolarization disorders. Cardiotoxic manifestations in two cases have been the vital threat for the patients. After application of nonspecific and symptomatic therapy, clinical and electrocardiographic signs of cardiotoxicity were withdrawn, that is, heart sequeles were not recorded.

[Neuroleptic malignant syndrome with rhabdomyolysis and muscle rupture]. / Neurolepticki maligni sindrom sa rabdomiolizom i rupturom misica.

We report a case of neuroleptic malignant syndrome (NMS) development after the ingestion of 960 mg of haloperidol in 18-year old male on the previous long-term neuroleptic treatment. Beside the severe rigidity and laboratory signs of rhabdomyolysis, firm swelling of gluteal and femoral areas, accompanied by pain and difficulty in the extension of the right leg, was noticed. The ultrasonography of the affected limb revealed partial rupture of quadriceps muscle. Since no signs of trauma or any other causes of muscle rupture were observed, we concluded that it developed due to the severe hypertonia and rhabdomyolysis in NMS. As there were no such cases previously reported, we wished to point out the possibility of muscle rupture development in NMS and propose the adequate diagnostic procedures and treatment.