Reference

Therapeutic dose range of nefazodone in the treatment of major depression

Therapeutic dose range of nefazodone in the treatment of major depression. Robinson, Donald S.; Marcus, Ronald N.; Archibald, Donald G.; Hardy, Sterling A. (Melbourne, FL, USA). Journal of Clinical Psychiatry, 57(Suppl. 2), 6-9 (English) 1996 Physicians Postgraduate Press. CODEN: JCLPDE. ISSN: 0160-6689. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review with 11 refs. The therapeutic dose range of nefazodone for treatment of major depression was examd. in a series of placebo-controlled efficacy studies carried out during phase 2 and 3 premarketing clin. evaluation. Nefazodone is a new antidepressant drug with pharmacol. effects on both serotonin and norepinephrine neurotransmitters. The usual starting dose of nefazodone for depressed patients, unless they are being switched from a serotonin selective reuptake inhibitor (SSRI), is 100 mg. b.i.d. A lower starting dose is recommended for elderly patients or patients being treated with an SSRI. Following assessment of the patient's clin. There are some commonly used reagents like 83366-66-9 in this article. response after the first week of therapy, the daily dose should be adjusted upward for most patients. In the efficacy studies, the majority of patients were being maintained on a dose of 300 to 500 mg daily at the end of the acute treatment period. The side effects of nefazodone most often related to dosage were sedation, nausea, and visual symptoms. Imipramine-treated patients, on the other hand, had a high incidence of dry mouth, constipation, and asthenia. In these studies, nefazodone was found to be effective and well tolerated by patients, the majority of whom were being maintained at a 300- to 500-mg/day dose, following an initial starting dose of 100 mg b.i.d. .

Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan

Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan. Barbhaiya, R. H.; Buch, A. B.; Greene, D. S. (Procter and Gamble, Cincinnati, OH, USA). British Journal of Clinical Pharmacology, 42(5), 573-581 (English) 1996 Blackwell. CODEN: BCPHBM. ISSN: 0306-5251. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The single and multiple dose pharmacokinetics of nefazodone (NEF) and its active metabolites hydroxynefazodone (HO-NEF) and m-chlorphenylpiperazine (mCPP) were evaluated in subjects classified as extensive metabolizers (EM) or poor metabolizers (PM) of dextromethorphan. In a parallel design study, 10 subjects from each phenotype received either 50 mg or 200 mg oral doses of NEF as single doses on Day 1 and multiple (twice daily) doses of Days 12-22. Serial plasma and urine samples were collected at specified time intervals after dosing on Days 1, 16, 18, 20 and 22. Plasma samples were analyzed for NEF, HO-NEF and mCPP. Urine samples were analyzed for mCPP and its metabolite p-hydroxy-mCPP (p-HO-mCPP) before and after hydrolyzing the samples with b-glucuronidase. For the 200mg dose group, the single dose plasma results showed no significant differences in pharmacokinetic parameters for NEF and HO-NEF in EM compared with PM subjects. However, for mCPP, Cmax was 89 ng ml-1 in the PM subjects compared with 44 ng ml-1 in the EM subjects, AUC was higher in the PM than EM subjects (1642 ng ml-1 h and 412 ng ml-1 h, resp.), and mCPP elimination half-life increased from 6.1 h in the EM subjects to 16.Several substances with their cas registry numbers 83366-66-9 and 125-71-3 may be metioned in this study.4 h in the PM subjects. Upon multiple dosing, plasma levels for NEF and all metabolites reached steady state within 3 days of dosing in both groups of subjects. Steady state pharmacokinetic parameters for NEF and HO-NEF in EM and PM subjects were not significantly different. The steady state Cmax and AUC values for mCPP in the PM subjects were 182 ng ml-1 and 1706 ng ml-1 h, resp., compared with 49.6 ng ml-1 and 182 ng ml-1 h in the EM subjects. The cumulative urinary excretion of mCPP and p-HO-mCPP was different for EM and PM subjects. Excretion of total mCPP and total p-HO-mCPP was approx. four-fold lower and five-fold higher, resp., in the EM subjects than PM subjects. These results indicate that the conversion of mCPP to p-HO-mCPP is attributable to metab. by cytochrome P 450 2D6. The differences in mCPP pharmacokinetic parameters in PM subjects did not effect the time required for NEF and its metabolites to attain steady state or the no. of adverse experiences in either group of subjects. Based on the results of this study, NEF may be dosed to EM and PM patients without regard to their cytochrome P 450 2D6 phenotype. .