Pharmacokinetics of dexamethasone and valspodar, a P-glycoprotein (mdr1) modulator: implications for coadministration

Pharmacotherapy. 1998 Nov-Dec;18(6):1230-6.


Study objective: To assess the potential for a drug-drug interaction between valspodar, a P-glycoprotein (mdrl) modulator used as a chemotherapy adjunct, and dexamethasone, widely included in oncology antiemetic regimens.

Design: Randomized, open-label, three-period crossover study.

Setting: Clinical pharmacology research center.

Subjects: Eighteen healthy men volunteers (age 25.8+/-3.5 yrs, weight 71.6+/-10.3 kg).

Interventions: Subjects received single fasting oral doses of valspodar 400 mg, dexamethasone 8 mg, and both drugs concomitantly with 2- to 3-week washout phases between administrations.

Measurements and main results: Lack of a pharmacokinetic drug-drug interaction with respect to valspodar was conclusively demonstrated for both Cmax,b (2.3+/-0.4 vs 2.4+/-0.5 microg/ml) and AUCb (19.8+/-4.8 vs 19.6+/-4.9 microg x hr/ml) inasmuch as bioequivalence criteria were satisfied when comparing administration alone with coadministration, respectively. Although no changes in the rate of dexamethasone absorption were noted on coadministration with valspodar (Cmax 88+/-23 vs 91+/-20 ng/ml), overall exposure was significantly increased by 24% on average (AUC 400+/-87 vs 494+/-90 ng x hr/ml). Regression analysis of valspodar Cmax,b and AUCb during coadministration versus the extent of the interaction (percentage increase in dexamethasone AUC) did not reveal a concentration-effect relationship (p=0.7299 and 0.9718, respectively).

Conclusion: Given dexamethasone's wide therapeutic index and the short duration of coadministration foreseen for these drugs in a clinical setting (maximum 1 wk/chemotherapy cycle), the 24% increase in dexamethasone's AUC is unlikely to be relevant. Thus no alterations in valspodar or dexamethasone dosages appear warranted when the two drugs are coadministered. Multiple-dose experience in patients would be desirable to confirm these conclusions.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
  • Adult
  • Antiemetics / adverse effects
  • Antiemetics / pharmacokinetics*
  • Area Under Curve
  • Cross-Over Studies
  • Cyclosporins / adverse effects
  • Cyclosporins / pharmacokinetics*
  • Dexamethasone / adverse effects
  • Dexamethasone / pharmacokinetics*
  • Drug Interactions
  • Extremities
  • Humans
  • Linear Models
  • Male
  • Paresthesia / chemically induced


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antiemetics
  • Cyclosporins
  • Dexamethasone
  • valspodar