Negligible impact of birth on renal function and drug metabolism

Abstract

Background: Transition from the intrauterine to the extrauterine environment in neonates is associated with major changes in blood flow and oxygenation with consequent increases in metabolic functions. The additional impact of birth on renal function and drug metabolism above that predicted by postmenstrual age and allometry is uncertain. Increased clearance at birth could reduce analgesic effect attributable to a lowering of plasma concentration. These elimination processes can be described using the clearance concept.

Methods: Data from four publications that investigated the time course of glomerular filtration rate and clearance of paracetamol, morphine and tramadol were reanalyzed. The effect of birth, based on postnatal age, was used in conjunction with a theory-based allometric size scaling and maturation based on postmenstrual age.

Results: Postnatal age had a short-term effect on the time course of clearance distinguishable from the well-known slower maturation based on postmenstrual age. While elimination might be relatively reduced by 15%-45% at birth, there is a rapid increase in elimination for 1-3 weeks after birth to be 15% greater than that predicted by postmenstrual age alone.

Conclusion: Birth is associated with a small increase in clearance in addition to that described by postmenstrual age for common analgesic drugs cleared by glucuronide conjugation (morphine, paracetamol) or by the P450 cytochrome oxidase (tramadol) and renal systems. While the increase is of biological interest, it would not be expected to have any clinically relevant impact on renal function or drug dosing. The processes of maturation described by these models are potentially applicable to any drug elimination process.

Keywords: birth; clearance; maturation; morphine; neonates; paracetamol; pharmacokinetics; renal function; tramadol.