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Related Concept Videos

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant

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In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
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Renal Failure: Dose Adjustments01:11

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In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
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Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

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It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
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Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration01:28

Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration

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Glomerular filtration rate (GFR) can be estimated from serum creatinine using the modification of diet in renal disease (MDRD) formula or the chronic kidney disease–epidemiology collaboration (CKD–EPI) equation. Both methods are widely used in clinical practice to assess kidney function and guide treatment decisions.The MDRD equation does not require weight or height measurements and is normalized to the body surface area of 1.73 m², considered the average adult surface area.
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Drug Dosing in Renal Diseases: Measurement of Serum Creatinine Concentration and Clearance01:25

Drug Dosing in Renal Diseases: Measurement of Serum Creatinine Concentration and Clearance

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In healthy individuals, serum creatinine levels remain stable due to a balance between its constant production—primarily from muscle metabolism—and renal excretion. Creatinine is freely filtered by the glomeruli, making it a valuable marker for estimating renal function. When the glomerular filtration rate (GFR) decreases, the kidneys can only eliminate less creatinine, causing serum levels to rise.Serum creatinine concentration is widely used to estimate creatinine clearance...
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Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

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Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
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Calvert Formula Modification for Optimized Carboplatin Dosing in Breast Cancer with Preserved Renal Function.

Jihyun Jeon1, Jiyeon Jeon1, Huong Tra Dang1

  • 1College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.

Pharmaceutics
|May 4, 2026
PubMed
Summary

The Calvert formula for carboplatin dosing in breast cancer is improved by using estimated glomerular filtration rate (eGFR) instead of creatinine clearance (CrCL). A modified formula showed further benefits, requiring prospective validation for clinical use.

Keywords:
Calvert formulabreast cancercarboplatinmeta-analysispopulation pharmacokinetic model

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Area of Science:

  • Oncology
  • Pharmacokinetics
  • Nephrology

Background:

  • The Calvert formula is standard for carboplatin dosing but may be inaccurate in specific patient groups.
  • Breast cancer patients with preserved renal function (CrCL ≥ 55 mL/min) require precise carboplatin dosing.
  • Evaluating and enhancing the accuracy of carboplatin dosing is crucial for treatment efficacy and safety.

Purpose of the Study:

  • To assess the adequacy of the conventional Calvert formula for carboplatin dosing.
  • To propose modifications to the Calvert formula for improved accuracy in breast cancer patients.
  • To evaluate carboplatin dose predictions using creatinine clearance (CrCL) versus estimated glomerular filtration rate (eGFR).

Main Methods:

  • A systematic review and meta-analysis of published pharmacokinetic models in breast cancer patients.
  • Integration of two retrospective datasets (n=154) for carboplatin dose calculation.
  • Comparison of conventional CrCL-based, eGFR-based, and modified Calvert formulas using predicted area under the curve (AUC).

Main Results:

  • Switching from CrCL to eGFR in the Calvert formula significantly improved target AUC attainment from 66.0% to 88.3%.
  • eGFR-based dosing reduced underexposure from 22.1% to 5.8% and overexposure from 4.5% to 0.65%.
  • A modified formula with an additional constant (α=1) further reduced underexposure but did not significantly alter target attainment or overexposure.

Conclusions:

  • Replacing CrCL with CKD-EPI-derived eGFR in the Calvert formula substantially enhances carboplatin dosing accuracy in breast cancer.
  • A modest structural modification to the formula provided additional benefits, warranting further investigation.
  • Adoption of eGFR-based dosing is supported, with a need for prospective validation of modified formulas using measured concentrations and clinical outcomes.