ArticleBritish journal of clinical pharmacology2013
Predicted metabolic drug clearance with increasing adult age.
Article in British journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Systematic review and meta-analysis of risk prediction models for anti-tuberculosis drug-induced liver injury in East Asian populations.Frontiers in public health · 2026Pooled it
- Effects of Caffeine Ingestion on Human Standing Balance: A Systematic Review of Placebo-Controlled Trials.Nutrients · 2021Pooled it
- Virtual Twin Approach Using Physiologically Based Pharmacokinetic Modeling to Support Precision Dosing of Valproic Acid in Geriatric Patients.Clinical pharmacology and therapeutics · 2026Article
- Optimizing therapeutic drug monitoring of mirtazapine - applying therapeutic reference range, concentration-dose ratio/dose-related concentration, and metabolic ratio in a naturalistic setting.European journal of clinical pharmacology · 2025Article
- A trajectory-informed model for detecting drug-drug-host interaction from real-world data.Journal of biomedical informatics · 2025Article
- Chemical exposomics in biobanked plasma samples and associations with breast cancer risk factors.Journal of exposure science & environmental epidemiology · 2025Article
- Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models.Pharmaceutics · 2025Article
- Application of Physiologically Based Pharmacokinetic Model to Delineate the Impact of Aging and Renal Impairment on Ceftazidime Clearance.Antibiotics (Basel, Switzerland) · 2024Article
- Central Nervous System Medications: Pharmacokinetic and Pharmacodynamic Considerations for Older Adults.Drugs & aging · 2024Review
- An insight into pharmacokinetics and dose optimization of antimicrobials agents in elderly patients.Frontiers in pharmacology · 2024Review
- Virtual twin for healthcare management.Frontiers in digital health · 2023Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Age-Related Change in Hepatic Clearance Inferred from Multiple Population Pharmacokinetic Studies: Comparison with Renal Clearance and Their Associations with Organ Weight and Blood Flow.Clinical pharmacokinetics · 2022Article
- Physiologically Based Pharmacokinetic Modelling to Identify Pharmacokinetic Parameters Driving Drug Exposure Changes in the Elderly.Clinical pharmacokinetics · 2020Article
- Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects.The pharmacogenomics journal · 2020Article
- The challenge of HIV treatment in an era of polypharmacy.Journal of the International AIDS Society · 2020Review
- Article
- Physiologically-based pharmacokinetics of ziprasidone in pregnant women.British journal of clinical pharmacology · 2019Article
- Repository Describing an Aging Population to Inform Physiologically Based Pharmacokinetic Models Considering Anatomical, Physiological, and Biological Age-Dependent Changes.Clinical pharmacokinetics · 2019Article
- Prescribing issues in older adults living with HIV: thinking beyond drug-drug interactions with antiretroviral drugs.Therapeutic advances in drug safety · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo determine the effect of increasing adult age on predicted metabolic drug clearance.
methodPredicted metabolic drug clearances (CLPT ) were determined using in vitro-in vivo extrapolation coupled with physiological-based pharmacokinetic modelling and simulation (IVIVE-PBPK) in Simcyp®. Simulations were conducted using CYP-selective 'probe' drugs with subjects in 5 year age groups (20-25 to 90-95 years). CLPT values were compared with human pharmacokinetic data stratified according to age (young = 20-40 years and elderly = 65-85 years) and gender. Age-related changes in the physiological parameters used for IVIVE of CLPT were described.
resultsPredicted metabolic drug clearances decreased with increasing adult age to approximately 65-70 years: caffeine from 1.5 to 1.0 ml min(-1) kg(-1) (a 33% decrease), S-warfarin from 0.100 to 0.064 ml min(-1) kg(-1) (36%), S-mephenytoin from 4.1 to 2.5 ml min(-1) kg(-1) (39%), desipramine from 10.6 to 7.3 ml min(-1) kg(-1) (31%) and midazolam from 5.4 to 3.9 ml min(-1) kg(-1) (27%). Except for S-mephenytoin, predictions were within 3.5-fold of clearances from clinical studies when stratified by age and gender. A trend towards higher CLPT was observed in females, but this was only statistically significant in larger virtual trials. Physiological parameters that determine CLPT decreased with increasing adult age: mean microsomal protein g(-1) of liver, liver weight, hepatic blood flow and human serum albumin concentration.
conclusionDecreased metabolic clearance in the elderly was predicted by Simcyp® and was generally consistent with limited clinical data for four out of five drugs studied and the broader literature for drugs metabolized by CYP enzymes. IVIVE-PBPK may be increasingly useful in predicting metabolic drug clearance in the elderly.
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