Negligible impact of birth on renal function and drug metabolism

Anderson, Brian J.; Holford, Nicholas H. G.

doi:10.1111/pan.13497

Cited by 15 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests immature glucuronidation of HM in the neonate that have to be considered when hydromorphone in labour analgesia is used. However, glomerular filtration rate in the neonates increases approximately 15% at birth and this increases slightly elimination of morphine and paracetamol [26], but we did not find data about hydromorphone elimination in newborns.…”

Section: Discussioncontrasting

confidence: 74%

Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure

Puhto

Kokki

Hakomäki

et al. 2020

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Introduction Epidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients. Materials and methods In this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone's effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS). Results All patients received additional levobupivacaine doses on parturients' requests. The first dose was requested at a median of 163 min (range 19-303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone's distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation. Conclusions The optimal dose of hydromorphone in labour pain warrants further evaluation.

show abstract

Section: Discussioncontrasting

confidence: 74%

Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure

Puhto

Kokki

Hakomäki

et al. 2020

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…After including BW and GA as fixed effects, clearance proved to be strongly dependent on PNA. This effect was much larger than can be expected from maturation alone 40 . Therefore, we hypothesized that this was caused by recovery of organ function after asphyxia.…”

Section: Discussionmentioning

confidence: 92%

“…This effect was much larger than can be expected from maturation alone. 40 Therefore, we hypothesized that this was caused by recovery of organ function after asphyxia. The effect of PNA was largest in the high-clearance compounds.…”

Section: Discussionmentioning

confidence: 99%

Prediction of Drug Exposure in Critically Ill Encephalopathic Neonates Treated With Therapeutic Hypothermia Based on a Pooled Population Pharmacokinetic Analysis of Seven Drugs and Five Metabolites

Favié

Haan

Bijleveld

et al. 2020

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Drug dosing in encephalopathic neonates treated with therapeutic hypothermia is challenging; exposure is dependent on body size and maturation but can also be influenced by factors related to disease and treatment. A better understanding of underlying pharmacokinetic principles is essential to guide drug dosing in this population. The prospective multicenter cohort study PharmaCool was designed to investigate the pharmacokinetics of commonly used drugs in neonatal encephalopathy. In the present study, all data obtained in the PharmaCool study were combined to study the structural system specific effects of body size, maturation, recovery of organ function, and temperature on drug clearance using nonlinear mixed effects modeling. Data collected during the first 5 days of life from 192 neonates treated with therapeutic hypothermia were included. An integrated population pharmacokinetic model of seven drugs (morphine, midazolam, lidocaine, phenobarbital, amoxicillin, gentamicin, and benzylpenicillin) and five metabolites (morphine‐3‐glucuronide, morphine‐6‐glucuronide, 1‐hydroxymidazolam, hydroxymidazolam glucuronide, and monoethylglycylxylidide) was successfully developed based on previously developed models for the individual drugs. For all compounds, body size was related to clearance using allometric relationships and maturation was described with gestational age in a fixed sigmoidal Hill equation. Organ recovery after birth was incorporated using postnatal age. Clearance increased by 1.23%/hours of life (95% confidence interval (CI) 1.03–1.43) and by 0.54%/hours of life (95% CI 0.371–0.750) for high and intermediate clearance compounds, respectively. Therapeutic hypothermia reduced clearance of intermediate clearance compounds only, by 6.83%/°C (95% CI 5.16%/°C–8.34%/°C). This integrated model can be used to facilitate drug dosing and future pharmacokinetic studies in this population.

show abstract

“…GFR in neonates can be assessed using endogenous or exogenous markers (1)(2)(3)(4)(5)(6)(7)(8). Among them, creatinine is the most widely used, although it is less accurate during the first days of life when its concentration reflects maternal levels (9).…”

Section: Introductionmentioning

confidence: 99%

Prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin as marker

Allegaert

Flint

et al. 2022

AAPS J

View full text Add to dashboard Cite

Describing glomerular filtration rate (GFR) maturation across the heterogeneous population of preterm and term neonates and infants is important to predict the clearance of renally cleared drugs. This study aims to describe the GFR maturation in (pre)term neonates and young infants (PNA < 90 days) using individual inulin clearance data (CLinulin). To this end, published GFR maturation models were evaluated by comparing their predicted GFR with CLinulin retrieved from literature. The best model was subsequently optimized in NONMEM V7.4.3 to better fit the CLinulin values. Our study evaluated seven models and collected 381 individual CLinulin values from 333 subjects with median (range) birthweight (BWb) 1880 g (580–4950), gestational age (GA) 34 weeks (25–43), current weight (CW) 1890 g (480–6200), postnatal age (PNA) 3 days (0–75), and CLinulin 2.20 ml/min (0.43–17.90). The De Cock 2014 model (covariates: BWb and PNA) performed the best in predicting CLinulin, followed by the Rhodin 2009 model (covariates: CW and postmenstrual age). The final optimized model shows that GFR at birth is determined by BWb, thereafter the maturation rate of GFR is dependent on PNA and GA, with a higher GA showing an overall faster maturation. To conclude, using individual CLinulin data, we found that a model for neonatal GFR requires a distinction between prenatal maturation quantified by BWb and postnatal maturation. To capture postnatal GFR maturation in (pre)term neonates and young infants, we developed an optimized model in which PNA-related maturation was dependent on GA. Graphical abstract

show abstract

Negligible impact of birth on renal function and drug metabolism

Cited by 15 publications

References 22 publications

Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure

Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure

Prediction of Drug Exposure in Critically Ill Encephalopathic Neonates Treated With Therapeutic Hypothermia Based on a Pooled Population Pharmacokinetic Analysis of Seven Drugs and Five Metabolites

Prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin as marker

Contact Info

Product

Resources

About