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 language | English (US) |
|---|---|
| Pages (from-to) | 281-286 |
| Number of pages | 6 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 40 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1986 |
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ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
Human pharmacokinetics of the antiviral drug DHPG. / Fletcher, Courtney; Sawchuk, Ronald; Chinnock, Barbara; de Miranda, Paulo; Balfour, Henry H.
In: Clinical Pharmacology and Therapeutics, Vol. 40, No. 3, 09.1986, p. 281-286.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human pharmacokinetics of the antiviral drug DHPG
AU - Fletcher, Courtney
AU - Sawchuk, Ronald
AU - Chinnock, Barbara
AU - de Miranda, Paulo
AU - Balfour, Henry H.
PY - 1986/9
Y1 - 1986/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0022551586&partnerID=8YFLogxK
U2 - 10.1038/clpt.1986.177
DO - 10.1038/clpt.1986.177
M3 - Article
C2 - 3017630
AN - SCOPUS:0022551586
VL - 40
SP - 281
EP - 286
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 3
ER -