ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Voriconazole has significant drug interactions due to metabolism by CYP enzymes. Subtherapeutic voriconazole concentrations associated with concomitant dexamethasone are not well described. CASE DESCRIPTION: An 84-year-old male was started on voriconazole for a fungal brain abscess. He was readmitted due to clinical failure thought to be the result of subtherapeutic voriconazole concentrations. Dexamethasone was identified as a potential cause due to its induction of CYP enzymes. This interaction was substantiated by sequential troughs that demonstrated a rise in voriconazole concentrations as dexamethasone was tapered off. WHAT IS NEW AND CONCLUSION: Therapeutic drug monitoring for patients on voriconazole and dexamethasone is essential to prevent suboptimal clinical outcomes.
ABSTRACT
This single-dose, open-label, parallel-group study compared the pharmacokinetics and tolerability of 120 mg doses of nateglinide, a physiologic mealtime glucose regulator for type 2 diabetes, in 8 subjects with cirrhosis and 8 matched healthy subjects. In both groups, plasma concentration peaked in a median of 0.5 hours, and mean terminal elimination half-lives were comparable. Mean +/- SD pharmacokinetic parameters in cirrhotic versus healthy subjects were slightly different (Cmax, 7.7 +/- 4.9 vs. 5.6 +/- 1.3 micrograms/ml; AUC(0-t), 18.5 +/- 7.5 vs. 14.2 +/- 2.1 micrograms.h/ml, respectively). Mean apparent total clearance and mean renal clearance in both groups were comparable. Mean protein-bound fractions were equivalent; binding appeared unaltered by metabolites. One cirrhotic and 2 healthy subjects each reported one adverse event. No statistically significant or clinically relevant alteration in pharmacokinetic parameters of nateglinide resulted from hepatic dysfunction, and it was well tolerated; therefore, adjustment of nateglinide dosage is not required in subjects with mild to moderate cirrhosis.
