Oral administration of taxanes

Oral treatment with cytotoxic agents is to be preferred as this administration route is convenient to patients, reduces administration costs and facilitates the use of more chronic treatment regimens. For the taxanes paclitaxel and docetaxel, however, low oral bioavailability has limited development of treatment by the oral route. Preclinical studies with mdr1a P-glycoprotein knock-out mice, which lack functional P-glycoprotein activity in the gut, have shown significant bioavailability of orally administered paclitaxel. Additional studies in wild-type mice revealed good bioavailability after oral administration when paclitaxel was combined with Pglycoprotein blockers such as cyclosporin A or the structurally related compound SDZ PSC 833. Based on the extensive preclinical research, the feasibility of oral administration of paclitaxel and docetaxel in cancer patients was recently demonstrated in our Institute. Co-administration of cyclosporin A strongly enhanced the oral bioavailability of both paclitaxel and docetaxel. For docetaxel in combination with cyclosporin A an oral bioavailability of 90% was achieved with an interpatient variability similar to that after intravenous drug administration; for paclitaxel the oral bioavailability is estimated at approximately 50%. The safety of the oral route for both taxanes is good. A phase II study of weekly oral docetaxel in combination with cyclosporin A is currently ongoing

Two cases of a pharmacokinetic interaction between (val)acyclovir and mycophenolate mofetil

Background: Administration of (val)acyclovir in combination with mycophenolate mofetil (MMF) can result in increased acyclovir plasma levels due to competition with acyclovir for renal tubular secretion. Several studies of pharmacokinetic interactions between acyclovir and MMF have been previously described, however, they present conflicting results. Case report: We present two cases of male patients to whom a pharmacokinetic interaction occurred between (val)acyclovir and mycophenolate mofetil. Results: Case A developed an acyclovir through level of 3.5 mg/L on day 3 of his acyclovir treatment, which resulted in neurotoxicity attributed to acyclovir overdosing because of the pharmacokinetic interaction with MMF. Case B developed an acyclovir through level of 3.2 mg/L on day 4 of his acyclovir treatment, which was attributed to the pharmacokinetic interaction with MMF in combination with his poor renal function. No adverse side-effects occurred. Conclusion: Clinical decision support systems should be used to generate alerts when (val)acyclovir and MMF are co-administered in patients with renal impairment (eGFR < 60 ml/min/1,73 m2). By using early-stage therapeutic drug monitoring, dosages can be adjusted if necessary