Influence of fluoxetine on olanzapine pharmacokinetics.

Conventional antidepressant treatment fails for up to 30% of patients with major depression. When there are concomitant psychotic symptoms, response rates are even worse. Thus, subsequent treatment often includes combinations of antidepressants or augmentation with antipsychotic agents. Atypical antipsychotic agents such as olanzapine cause fewer extrapyramidal adverse effects than conventional antipsychotics; for that reason, they are an advantageous augmentation strategy for treatment-resistant and psychotic depression. The purpose of this study was to assess the potential for pharmacokinetic interaction between olanzapine and fluoxetine, a popular antidepressant that is a selective serotonin reuptake inhibitor. The pharmacokinetics of 3 identical single therapeutic doses of olanzapine (5 mg) were determined in 15 healthy nonsmoking volunteers. The first dose of olanzapine was taken alone, the second given after a single oral dose of fluoxetine (60 mg), and the third given after 8 days of treatment with fluoxetine 60 mg, qd. Olanzapine mean Cmax was slightly higher (by about 18%) and mean CL/F was slightly lower (by about 15%) when olanzapine was coadministered with fluoxetine in single or multiple doses. Olanzapine mean t((1/2)) and median t(max) did not change. Although the pharmacokinetic effects of fluoxetine on olanzapine were statistically significant, the effects were small and are unlikely to modify olanzapine's safety profile. The mechanism of influence is consistent with an inhibition of CYP2D6, which is known to control a minor pathway of olanzapine metabolism.

Laparoscopical insertion of intraperitoneal catheters for intraperitoneal chemotherapy.

BACKGROUND AND METHODS: Eight patients (seven clinically negative stage Ill ovarian cancer and one peritoneal mesothelioma) respectively underwent second-look laparoscopy for staging, adhesiolysis and insertion of an intraperitoneal catheter and fixation of a portal. All patients had received six courses of cisplatin-paclitaxel-based chemotherapy intravenously. At the end of the laparoscopic staging, a 5-mm catheter was inserted under direct vision through a 5-mm trocar in the abdomen. A preaponevrotic forceps was used to grasp the catheter and bring it to the portal, which is located on the intercostal aponevrosis 2 or 3 cm above the laparoscope entry. RESULTS: Although previously operated, laparoscopy was possible in all patients and the catheters were easily inserted. All patients received intraperitoneal chemotherapy on the second postoperative day. We did not observe any complication after a mean follow-up of 12 months. CONCLUSIONS: Laparoscopic insertion of intraperitoneal catheters is a feasible and safe procedure but requires experience in laparoscopic surgery. In many cases it might preclude from performing non-useful laparotomies. It might help to reduce the hospital stay and the morbidity in relation to second-look laparotomies. Compared with the blind surgical technique of insertion of intraperitoneal catheters, this technique also allows intraabdominal staging. Nevertheless, further studies are necessary to confirm our results.