Chronical Kidney Disease (CKD) causes deterioration of renal function with reduction of glomerular filtration (GFR). Drugs which are mainly excreted through the kidney have reduced renal elimination (Clrenal) in CKD. For decades dosage adjustments for these drugs have been computed based on GFR measured by the clearance of serum creatinine (Clcr) and according to the rule of Dettli where the appropriate dose D compared to the normal dose (Dnorm) may be assessed through the individual elimination fraction Q:
Q = Qo + (1 – Qo) * GFR / 100
Qo = extrarenal elimination fraction
D = Dnorm * Q
Renal clearance through GFR is not the only mechanism which has an impact on renal drug elimination. There is also clearance by tubular secretion (Cls) and there are clinical findings which indicate that the linear Dettli formula is not powerful enough to compute dosing recommendations in the more complex scenario when GFR and Cls do not go parallel. A more appropriate formula to compute Q has been developed by SCHOLZ Databank Founder and Editor Wolfgang Scholz:
Q = Qo + (1 – Qo) * (a * GFR + b * GFR² ) / (a * 100 + b * 100² )
Please read the derivation of this enhanced Dettli formula in the full article published in the Austin Journal of Pharmacology and Therapeutics of October 2024. In particular, when the renal clearance of drugs depends on both GFR and Cls and the therapeutic index is narrow dosing assessments should be made as precise as possible to avoid serious adverse effects; this applies for example in the case of metformin which has a high risk of dangerous lactatacidosis when overdosed in renal failure.
Q = Qo + (1 – Qo) * GFR / 100
Qo = extrarenal elimination fraction
D = Dnorm * Q
Renal clearance through GFR is not the only mechanism which has an impact on renal drug elimination. There is also clearance by tubular secretion (Cls) and there are clinical findings which indicate that the linear Dettli formula is not powerful enough to compute dosing recommendations in the more complex scenario when GFR and Cls do not go parallel. A more appropriate formula to compute Q has been developed by SCHOLZ Databank Founder and Editor Wolfgang Scholz:
Q = Qo + (1 – Qo) * (a * GFR + b * GFR² ) / (a * 100 + b * 100² )
Please read the derivation of this enhanced Dettli formula in the full article published in the Austin Journal of Pharmacology and Therapeutics of October 2024. In particular, when the renal clearance of drugs depends on both GFR and Cls and the therapeutic index is narrow dosing assessments should be made as precise as possible to avoid serious adverse effects; this applies for example in the case of metformin which has a high risk of dangerous lactatacidosis when overdosed in renal failure.