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Related Concept Videos

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 Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

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Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
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Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

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In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
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Pharmacokinetics: Overview01:10

Pharmacokinetics: Overview

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Pharmacokinetics is a scientific discipline that focuses on the journey of a drug within the body, encompassing four key stages: absorption, distribution, metabolism, and elimination. The first stage, absorption, involves the drug's transfer into the bloodstream. Several factors dictate the extent and speed of this process. For example, the liver often metabolizes oral drugs before they reach systemic circulation, leading to only partial absorption. In contrast, intravenous (IV)...
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Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection00:59

Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection

166
In pharmacokinetics, the elimination rate of a drug following a capacity-limited model is primarily controlled by two parameters: Vmax and KM. These parameters are crucial in how the drug behaves inside the body after administration.
Following the administration of a single intravenous (IV) bolus injection, we can determine the concentration of the drug in the plasma at any given time. This calculation is achieved using a specific equation that integrates the values of Vmax and KM.
We can also...
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Renal Failure: Dose Adjustments01:11

Renal Failure: Dose Adjustments

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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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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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Ifosfamide pharmacokinetics.

L D Lewis1

  • 1Division of Clinical Pharmacology, Johns Hopkins Hospital, Baltimore, Maryland.

Investigational New Drugs
|November 1, 1991
PubMed
Summary
This summary is machine-generated.

This review details ifosfamide pharmacokinetics in chemotherapy. Ifosfamide metabolites, not the parent drug, likely cause neurotoxicity, suggesting optimized dosing strategies.

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Area of Science:

  • Pharmacology
  • Oncology
  • Drug Metabolism

Background:

  • Ifosfamide is a widely used chemotherapeutic agent, often associated with significant toxicities.
  • Understanding its pharmacokinetic profile is crucial for optimizing treatment efficacy and safety.
  • Cyclophosphamide congener ifosfamide requires detailed pharmacokinetic analysis across various regimens.

Purpose of the Study:

  • To review and detail the pharmacokinetics of ifosfamide.
  • To discuss the influence of administration route, schedule, and dose on ifosfamide pharmacokinetics.
  • To explore the relationship between ifosfamide pharmacokinetics and associated neurotoxicity.

Main Methods:

  • Review of existing literature on ifosfamide pharmacokinetics.
  • Analysis of pharmacokinetic data from various chemotherapeutic regimens.
  • Comparison of ifosfamide pharmacokinetics in patients with and without neurotoxicity.

Main Results:

  • Fractionated oral and intravenous ifosfamide therapy show time-dependent increases in metabolic clearance.
  • Ifosfamide pharmacokinetics are not dose-dependent (zero-order) at 5 g/m2 via short or long infusions.
  • Aberrant parent ifosfamide pharmacokinetics were not observed in patients with ifosfamide/mesna associated CNS toxicity.

Conclusions:

  • Ifosfamide metabolites are implicated as the primary cause of neurotoxicity, rather than the parent drug.
  • Further development of analytical methods for ifosfamide metabolites is needed.
  • Optimizing the therapeutic index of ifosfamide treatment may be achievable through metabolite-focused studies.