Potential for Interactions between Caspofungin and Nelfinavir or Rifampin

Stone, Julie A.; Migoya, Elizabeth; Hickey, Lisa; Winchell, Gregory A.; Deutsch, Paul; Ghosh, Kalyan; Freeman, Amanda; Bi, Sheng; Desai, Rajesh; Dilzer, Stacy C.; Lasseter, Kenneth C.; Kraft, Walter K.; Greenberg, Howard E.

doi:10.1128/aac.48.11.4306-4314.2004

Cited by 95 publications

(57 citation statements)

References 17 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…On the basis of the final PopPK model of the present study, simulated steady-state AUC values at a dose level of 100 mg together with historical data after multiple administrations of 15-to 100-mg doses of CAS (10,21,31,(34)(35)(36) are shown in Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Würthwein

Cornely

Trame

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

g Caspofungin (CAS) is approved for second-line management of proven or probable invasive aspergillosis at a dose of 50 mg once daily (QD). Preclinical and limited clinical data support the concept of the dose-dependent antifungal efficacy of CAS with preservation of its favorable safety profile. Little is known, however, about the pharmacokinetics (PKs) of higher doses of CAS in patients. In a formal multicenter phase II dose-escalation study, CAS was administered as a 2-h infusion at doses ranging from 70 to 200 mg QD. CAS PK sampling (n ‫؍‬ 468 samples) was performed on day 1 and at peak and trough time points on days 4, 7, 14, and 28 (70 mg, n ‫؍‬ 9 patients; 100 mg, n ‫؍‬ 8 patients; 150 mg, n ‫؍‬ 9 patients; 200 mg, n ‫؍‬ 20 patients; total, n ‫؍‬ 46 patients). Drug concentrations in plasma were measured by liquid chromatography tandem mass spectroscopy. Population pharmacokinetic analysis (PopPK) was performed using NONMEM (version 7) software. Model evaluation was performed using bootstrap analysis, prediction-corrected visual predictive check (pcVPC), as well as standardized visual predictive check (SVPC). The four investigated dose levels showed no difference in log-transformed dose-normalized trough levels of CAS (analysis of variance).

show abstract

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Würthwein

Cornely

Trame

et al. 2013

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…99 Genetic polymorphisms of OATP1B1 100 may affect the efficiency of uptake of caspofungin into the liver. However, there are no other known points at which genetic variability affects caspofungin, and hence pharmacogenomic analysis will be of minor importance in optimising use of this antifungal drug.…”

Section: Echinocandinsmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

View full text Add to dashboard Cite

“…Results from a clinical study conducted by Stone et al (2004) suggested that RIF both induced and inhibited the disposition of caspofungin, which has been shown to be a substrate of OATP1B1 (Sandhu et al, 2005). In another clinical study, when RIF and repaglinide were coadministered, RIF acted as an inducer and inhibitor of repaglinide metabolism (Bidstrup et al, 2004).…”

mentioning

confidence: 99%

Elucidating the Effect of Final-Day Dosing of Rifampin in Induction Studies on Hepatic Drug Disposition and Metabolism

Lam¹,

Shugarts²,

Okochi³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Because rifampin (RIF) induces hepatic enzymes and inhibits uptake transporters, dosing a drug that is a dual substrate of enzymes and uptake transporters on the final day of an inducing regimen should exhibit less inductive effect than dosing on the following day in the absence of RIF, since RIF decreases drug uptake into liver. In vitro and in vivo rat studies were conducted using digoxin as a model substrate. Digoxin was administered to an uninduced control group to obtain baseline values. The second group (induced with dexamethasone) received digoxin alone, mimicking administration of a test drug 1 day following completion of an induction regimen, whereas the third group (induced) received digoxin with RIF mimicking the concomitant dosing on the final day of an induction regimen. Results from hepatocyte concentration-time course studies showed that compared with uninduced control (26.9 Ϯ 1.3 M ⅐ min/mg), digoxin area under the time-concentration curve (AUC) in induced cells when no RIF is present decreased significantly (13.7 Ϯ 0.9 M ⅐ min/mg; p Ͻ 0.01), suggesting induction of Cyp3a. However, digoxin AUC for induced cells in the presence of RIF (27.3 Ϯ 0.9 M ⅐ min/mg) matched the control. Rat pharmacokinetic studies showed that compared with digoxin clearance in uninduced controls (7.08 Ϯ 1.57 ml/min/kg), digoxin clearance in induced rats increased 2-fold (15.6 Ϯ 3.7 ml/min/kg; p Ͻ 0.001), but when RIF was coadministered in the induced rats, digoxin clearance (7.14 Ϯ 1.24 ml/min/kg) overlapped with control. That is, concomitant dosing of RIF and digoxin masked the inductive effect. To observe full inductive effects, test drugs should be administered 1 day after final dosing of RIF to minimize potential organic anion transporting polypeptide inhibition effects.

show abstract

Potential for Interactions between Caspofungin and Nelfinavir or Rifampin

Cited by 95 publications

References 17 publications

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Elucidating the Effect of Final-Day Dosing of Rifampin in Induction Studies on Hepatic Drug Disposition and Metabolism

Contact Info

Product

Resources

About