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Ozdemir, V. et al.

The extent and determinants of changes in CYP2D6 and CYP1A2 activities with therapeutic doses of sertraline.

The extent of changes in CYP2D6 and CYP1A2 activities with higher therapeutic dosages (>50 mg/day) of sertraline is not well established in vivo. This study assessed the extent and determinants of changes in CYP2D6 and CYP1A2 isozyme activities after treatment with clinically relevant doses of sertraline. Patients and healthy volunteers aged 19 to 85 years (N = 21) were treated with sertraline for 5 to 55 days. The dosage of sertraline ranged from 25 to 150 mg/day (93.5+/-26.4 mg/day; mean +/- SD). All subjects had an extensive metabolizer phenotype for CYP2D6 and received a single oral dose of dextromethorphan (30 mg) and caffeine (100 mg) before and after sertraline treatment. The log O-demethylation ratio (ODMR) of dextromethorphan and the caffeine metabolic ratio (CMR) in overnight urine were used as in vivo indices of the CYP2D6 and CYP1A2 isozyme activities, respectively. Concurrent medications and lifestyle habits (e.g., smoking and diet) were monitored during the study. Baseline log ODMR (-2.33+/-0.45) but not CMR (5.1+/-1.9) (mean +/- SD) significantly changed after sertraline treatment (-2.19+/-0.62; 4.5+/-1.6, respectively) (p: ODMR = 0.04, CMR = 0.10). There was no significant effect of age, dose, duration of treatment, gender, sertraline and/or desmethylsertraline plasma concentration, subject type (patient or volunteer), and weight on the extent of changes in log ODMR or CMR (p > 0.05). In conclusion, sertraline treatment at a mean daily dosage of 94.0 mg did not significantly change CYP1A2 activity and resulted in a modest inhibition of CYP2D6 activity.[1]

References

The extent and determinants of changes in CYP2D6 and CYP1A2 activities with therapeutic doses of sertraline. Ozdemir, V., Naranjo, C.A., Herrmann, N., Shulman, R.W., Sellers, E.M., Reed, K., Kalow, W. Journal of clinical psychopharmacology. (1998) [Pubmed]

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