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Related Concept Videos

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion01:18

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion

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In geriatric patients, renal physiology undergoes significant changes, including diminished renal blood flow and a lower glomerular filtration rate (GFR), leading to alterations in medication clearance. Drugs such as aminoglycoside antibiotics, lithium, and digoxin, which rely on glomerular filtration for removal from the body, particularly impact pharmacokinetics. These drugs tend to have slower clearance rates in older adults, necessitating careful dosage considerations.Evaluation of renal...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Absorption01:22

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Absorption

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As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism01:18

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism

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Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
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Renal Drug Excretion: Glomerular Filtration01:02

Renal Drug Excretion: Glomerular Filtration

869
The kidney serves as the primary organ responsible for eliminating drugs and their metabolites from the body. This process, known as renal elimination, starts with glomerular filtration and results in urine formation. Each kidney houses millions of functional units called nephrons, where urine production occurs. A nephron has two main components: a renal corpuscle and a renal tubule.
Drugs gain access to the kidney via the renal artery, which progressively branches off into afferent arterioles....
869
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

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Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
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Factors Affecting Renal Clearance: Renal Impairment01:17

Factors Affecting Renal Clearance: Renal Impairment

273
Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
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A real or apparent decrease in glomerular filtration rate in patients using olaparib?

M A C Bruin1, C M Korse2, B van Wijnen2

  • 1Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. ma.bruin@nki.nl.

European Journal of Clinical Pharmacology
|December 15, 2020
PubMed
Summary

Olaparib increases creatinine levels by inhibiting renal transporters, not by reducing kidney function. Cystatin C is a more accurate marker for estimating glomerular filtration rate (GFR) in patients taking olaparib.

Keywords:
CreatinineCystatin COlaparibRenal functioneGFR

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Area of Science:

  • Oncology
  • Nephrology
  • Pharmacology

Background:

  • Olaparib, a PARP inhibitor, is used for ovarian and metastatic breast cancer.
  • Elevated serum creatinine in olaparib users suggests potential kidney effects, but the mechanism is unclear.

Purpose of the Study:

  • To determine if olaparib treatment increases creatinine levels.
  • To assess if observed creatinine increases correlate with reduced glomerular filtration rate (GFR).

Main Methods:

  • Retrospective analysis of 66 patients treated with olaparib.
  • Measured serum creatinine and cystatin C levels at baseline and during treatment.
  • Calculated estimated GFR (eGFR) using both creatinine and cystatin C based equations.

Main Results:

  • Olaparib treatment increased median creatinine by 14% and decreased creatinine-based eGFR by 13%.
  • No significant changes were observed in median cystatin C levels or cystatin C-based eGFR.
  • This indicates olaparib affects creatinine levels independently of GFR.

Conclusions:

  • Olaparib likely inhibits renal transporters, causing a reversible increase in creatinine.
  • Creatinine-based eGFR may underestimate true GFR in olaparib patients.
  • Cystatin C is recommended for accurate eGFR assessment in patients receiving olaparib.