Human pharmacokinetics of the antiviral drug DHPG

Courtney Fletcher, Ronald Sawchuk, Barbara Chinnock, Paulo de Miranda, Henry H. Balfour

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-l-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t 1 2 of 0.23 hours and terminal t 1 2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 μg/ml and <0.25 to 0.63 μg/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.

Original languageEnglish (US)
Pages (from-to)281-286
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume40
Issue number3
DOIs
StatePublished - Sep 1986

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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