Mary F. Hebert

Aims Previously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne. Methods Thirty‐three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual‐probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre‐isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2‐h postdose plasma samples and in cumulative 0‐4‐h urine collections using liquid chromatography‐mass spectrometry. Results In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre‐isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3‐hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX‐O‐glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre‐isotretinoin. Conclusions Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.

Complications throughout the peripartum period may be caused by preexisting conditions or pregnancy-induced conditions and may alter pharmacotherapy management. Pharmacotherapy management during late pregnancy and delivery requires careful consideration due to changing hormones, hemodynamic status, and pharmacokinetics, and concerns for potential maternal and/or fetal morbidity. Increased maternal and fetal monitoring are often required and may lead to therapy changes. Pharmacists, as key members of the interprofessional team, can contribute essential perspective to the management of postpartum pharmacotherapy through assessment and recommendation of appropriate and judicious use of medications.