Pharmacokinetics of valganciclovir and ganciclovir in renal impairment

Abstract

The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.

Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir

“…Derived parameters such as absorption and elimination halflife are also congruent with previous observations (1,6,32). Our population of patients is characterized by a wide range of renal function (GFR C-G range, 10 to 170 ml/min), leading to a comparable range of elimination half-life values.…”

“…The estimated parameters were the systemic clearance (CL), the intercompartmental clearance (Q), the central volume of distribution (V 1 ), the peripheral volume of distribution (V 2 ), and the absorption rate constant (k a ). Since GCV was administered intravenously only in two patients, the bioavailability (F) could not be estimated with sufficient accuracy and was fixed at 0.6 according to previous studies (6,10,19,24). Derived parameters were the absorption half-life [t 1/2a ϭ ln(2)/k a ] and the elimination half-life [t 1/2␤ ϭ ln(2)/ ␤ , with ␤ derived from CL, Q, V 1 , and V 2 ].…”

“…GCV administered as VGC is characterized by a 10-fold-higher oral bioavailability (6,10,19,24), with a VGC dose of 900 mg once daily providing a systemic exposure comparable to that of intravenous GCV at 5 mg/kg (6,19,24). The efficacy of GCV delivered as VGC has been established for the prevention of cytomegalovirus (CMV) disease in kidney, heart, and kidney-pancreas recipients at high risk for developing it (i.e., CMV-seropositive donor/CMV-seronegative recipient [Dϩ/RϪ]) (21) and recently for the treatment of CMV disease in organ transplant recipients (2).…”

“…Thus, in renal insufficiency, the dosage of VGC has to be adjusted to the estimated glomerular filtration rate (GFR) (6). GCV is secreted through the organic anion transporters (OAT) (14) and therefore at risk for drug interactions with transport inhibitors.…”

Role of Therapeutic Drug Monitoring in Pulmonary Infections: Use and Potential for Expanded Use of Dried Blood Spot Samples

“…These 349 drugs are not extensively metabolised, but are subject to renal elimination and dose adjustment for 350 patients with renal impairment is necessary [43,52]. Because of their lack of hepatic metabolism, 351…”