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Pharmacokinetics of ganciclovir in renal transplant children
E Jacqz-Aigrain1, M A Macher, H Sauvageon-Marthe
1Department of Clinical Pharmacology, Hôpital Robert-Debré, Pairs, France.
Insights
Pediatric kidney transplant patients receiving ganciclovir (DHPG) for cytomegalovirus (CMV) infection require careful dosage adjustments. Monitoring drug levels is crucial for effective treatment and to minimize toxicity in these vulnerable patients.
Area of Science:
- * Pediatric Nephrology
- * Transplant Immunology
- * Infectious Diseases
Background:
- * Cytomegalovirus (CMV) infection is a significant risk following solid organ transplantation, particularly in pediatric recipients.
- * Renal transplant recipients are susceptible to CMV disease, especially when receiving organs from seropositive donors.
Observation:
- * Three CMV-seronegative children developed CMV infection 20-34 days post-renal transplant from CMV-seropositive donors.
- * Ganciclovir (DHPG) was administered intravenously, with dosing adjusted for renal insufficiency based on adult recommendations.
Findings:
- * Individual pharmacokinetic parameters of DHPG were significantly altered in pediatric renal transplant recipients.
- * Plasma clearance and elimination half-life of DHPG correlated with individual creatinine clearance, indicating altered drug metabolism.
- * Dose reductions were necessary in two patients to maintain therapeutic plasma levels, highlighting variability in drug response.
Implications:
- * Standard adult dosing guidelines for ganciclovir may not be appropriate for pediatric renal transplant recipients.
- * Therapeutic drug monitoring of ganciclovir is essential to optimize efficacy and minimize toxicity in this population.
- * Further research is needed to establish precise dosing protocols for ganciclovir in pediatric transplant patients with varying degrees of renal function.
Abstract:
Three cytomegalovirus (CMV)-seronegative children received renal transplants from CMV-seropositive donors and developed clinical symptoms of CMV infection between days 20 and 34 post transplantation. Ganciclovir (DHPG) was administered in a 1-h infusion, and the doses and dose intervals were adapted to the degree of renal insufficiency, according to the manufacturer's recommendations for adults. Individual pharmacokinetic parameters of DHPG were determined and were markedly altered. Plasma clearances were 0.4, 1.1 and 2.2 ml/min per kg and were related to individual creatinine clearances (20, 45 and 60 ml/min per 1.73 m2); the corresponding elimination half-lives were 23.7, 9.9 and 3.9 h. In two patients, the doses had to be further reduced in order to maintain plasma levels within the recommended values for peak and trough plasma concentrations. Therefore, monitoring of DHPG appears essential in adjusting dosage for optimal efficacy and minimal toxicity.