Pharmacokinetic (PK) and pharmacodynamic (PD) interaction between nefazadone (NEF) and terfenadine (TER) but not NEF and loratidine (LOR)

D. R. Abernethy, J. Barbey, J. Franc, I. Ferreira, N. Ford, D. E. Salazar

Research output: Contribution to journalArticlepeer-review

Abstract

Sixty-seven healthy volunteers received NEF + placebo (PBO) (n=13), NEF + TER (n=14), NEF + LOR (n=14), TER + PBO (n=13) in a multiple dose study. PK: NEF increased TER AUC (ng·hr/ml) markedly and increased LOR AUC (ng·hr/ml) to a lesser extent. PBO (mean±SD) NEF p-value TER AUC 17.3±8.5 97.4±48.9 <.001 LOR AUC 31.5±27.9 43.7·25.9 .014 PD: NEF + TER markedly increased mean QTc prolongation associated with TER and NEF + LOR had little mean QTc prolongation, as did NEF + PBO and LOR + PBO. Mean QTc Prolongation (msec) 95% C.I. TER+NEF 42.4 (34.2,50.6) TER+PBO 8.0 (-0.6,16.6) LOR+NEF 21.6 (13.7,29.4) LOR+PBO 9.1 (1.1,17.1) NEF+PBO 10.8 (2.6,19.0) Conclusion: Coadministration of NEF with TER results in markedly increased exposure to TER and this is associated with increased QTc prolongation. Coadministration of NEF with LOR results in a limited increase in LOR exposure and this has a limited effect on QTc prolongation.

Original languageEnglish (US)
Pages (from-to)170
Number of pages1
JournalClinical pharmacology and therapeutics
Volume65
Issue number2
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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