A Concept for Pharmacokinetic- Pharmacodynamic Dosage Adjustment in Renal Impairment

Abstract

The parameter AUETC could be a useful pharmacokinetic-pharmacodynamic surrogate marker for dosage adjustment in renal impairment. Using the AUETC method, the beneficial effect can be balanced against the adverse effect.

Comparison of gentamicin dose estimates derived from manual calculations, the Australian ‘Therapeutic Guidelines: Antibiotic’ nomogram and the SeBA‐GEN and DoseCalc software programs

“…This method was adapted from Begg et al. [4] and was based on the premise that clearance of gentamicin is related to creatinine clearance [13, 14]. The manual calculation method compared favourably with SeBA‐GEN dose estimates in patients with moderate renal impairment (Table 3) but it underestimated the gentamicin dose in patients with mild or no renal impairment.…”

“…Thus, in the patients where gentamicin clearance was underestimated (usually those with mild or no renal impairment), the calculated AUC would have been overestimated, leading to prediction of a lower dose. Hence, alternatives to our equation 3 could be used (for example, CL Gm [ml min −1 ] = 2 + 77 × CL Cr /100 [14]), and the volume of distribution could be varied for specific patient groups [5, 14, 15]. Although the predicted dose from the manual calculation method was almost 40% lower than the SeBA‐GEN estimate in normal renal function, in patients with mild renal impairment the manual method underestimated the dose by only 10% (Table 3).…”

“…The manual method of dosage estimation was evaluated in this study, because of its potential value as an alternative (or back-up) to software packages and as an educational tool for practitioners who will routinely use nomograms or software applications. This method was adapted from Begg et al [4] and was based on the premise that clearance of gentamicin is related to creatinine clearance [13,14]. The manual calculation method compared favourably with SeBA-GEN dose estimates in patients with moderate renal impairment ( Table 3) but it underestimated the gentamicin dose in [14]), and the volume of distribution could be varied for specific patient groups [5,14,15].…”

“…This method was adapted from Begg et al [4] and was based on the premise that clearance of gentamicin is related to creatinine clearance [13,14]. The manual calculation method compared favourably with SeBA-GEN dose estimates in patients with moderate renal impairment ( Table 3) but it underestimated the gentamicin dose in [14]), and the volume of distribution could be varied for specific patient groups [5,14,15]. Although the predicted dose from the manual calculation method was almost 40% lower than the SeBA-GEN estimate in normal renal function, in patients with mild renal impairment the manual method underestimated the dose by only 10% (Table 3).…”

Pharmacokinetics of valganciclovir and ganciclovir in renal impairment

“…21,23 A pharmacokinetic model can be helpful for calculating dosage adjustments for patients with renal impairment. 24,25 The purpose of this study was (1) to look into the effect of renal impairment on the pharmacokinetics of ganciclovir after oral administration of valganciclovir, (2) to investigate the effects of hemodialysis on the pharmacokinetics of ganciclovir after valganciclovir, and (3) to compare the bioavailability of ganciclovir from valganciclovir in HIV/CMV-positive patients and healthy subjects with normal renal function.…”