Phenytoin-Isoniazid Interaction: A Kinetic Approach to Management

Witmer, David R.; Ritschel, W. A.

doi:10.1177/106002808401800607

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…Clint= Clearance interval; S=Substrate; Css-Steady-state concentration of drug;Clu-Urinary clearance; Vd=Volume of distribution; Inhibitory concentration 50; Jmax=Maximal carriermediated flux; Co=Initial donor concentration of the substance; Km=Metabolism constant (Grandvuinet et al, 2012).At Css where metabolism is saturated, enzyme velocity approaches Vmax. (Witmer and Ritschel, 1984). Equation xxi is referred to as specific growth function in cell growth modeling (Markov, 2013).…”

Section: Micjaelis-menten and Related Equationsmentioning

confidence: 99%

“…Most enzymes follow Michaelis -Menten kinetics (Montiet al,2017). But Phenytoin-isoniazid interaction could be managed using pharmacokinetic method of Michaelis -Menten order with in normal range and km increased by five-fold (Witmer and Ritschel, 1984). Clofazimine and prothionamide may cause drug-drug interaction when coadminsteredwith compounds metabolized by CYP 3A4and CYP2B6, respectively.Whereas isoniazid and rifapentine may cause drug-drug interaction with drugs metabolized by CYP3A4 (Shimokawaet al,2015).…”

Section: Drug-receptor Binding Affinity Is a Function Of Michaelis-mementioning

confidence: 99%

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Application of Modified Michaelis – Menten Equations for Determination of Enzyme Inducing and Inhibiting Drugs

Saganuwan

2020

Preprint

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Pharmacokinetics is the process of absorption, distribution, metabolism and elimination (ADME) of drugs. Some drugs undergo zero-order kinetics (e.g. ethyl alcohol,) first order kinetics (e.g. piroxicam) and mixed order kinetics (e.g. ascorbic acid). Drugs that undergo Michaelis-Menten metabolism are characterized by either increased or decreased Km and Vmax. Hence literatures were searched with a view to translating in vitro-in vivo enzyme kinetics to pharmacokinetic/pharmacodynamic parameters for determination of enzyme inducing and inhibiting drugs inorder to achieve optimal clinical efficacy and safety. Findings have shown that theophylline, voriconazole, phenytoin, thiopental, fluorouracil, thyamine and thymidine are enzyme inducers whereas mibefradil , metronidazole isoniazid and puromicin are enzyme inhibitors. They are metabolized and eliminated according to Michaelis-menten principle. The order could be mixed but may change to zero or first order depending on drug concentrations and frequency of drug administration. Hence, pharmacokinetic-pharmacodynamic translation can be optimally achieved by incorporating newly derived Michaelis-Menten equations into pharmacokinetic parameters for clinical efficacy and safety of therapeutics.

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Section: Micjaelis-menten and Related Equationsmentioning

confidence: 99%

Section: Drug-receptor Binding Affinity Is a Function Of Michaelis-mementioning

confidence: 99%

Application of Modified Michaelis – Menten Equations for Determination of Enzyme Inducing and Inhibiting Drugs

Saganuwan

2020

Preprint

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“…Most enzymes follow Michaelis – Menten kinetics [ 89 ]. Phenytoin- isoniazid interaction could be managed using pharmacokinetic method of Michaelis – Menten order with V max in normal range and Km increased by five- fold [ 49 ]. Clofazimine and prothionamide may cause drug-drug interaction when co-adminstered with compounds metabolized by CYP 3A4 and CYP2B6, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Clint = Intrinsic clearance; S=Substrate; Css- Steady-state concentration of drug;Clu-Urinary clearance; Vd = Volume of distribution; Inhibitory concentration 50; Jmax = Maximal carrier-mediated flux; Co = Initial donor concentration of the substance; Km = Metabolism constant [ 16 ]. At Css where metabolism is saturated, enzyme velocity approaches Vmax [ 49 ]. Therefore eqs.…”

Section: Methodsmentioning

confidence: 99%

Application of modified Michaelis – Menten equations for determination of enzyme inducing and inhibiting drugs

Saganuwan

2021

BMC Pharmacol Toxicol

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Background Pharmacokinetics (PK) is the process of absorption, distribution, metabolism and elimination (ADME) of drugs. Some drugs undergo zero-order kinetics (ethyl alcohol), first order kinetics (piroxicam) and mixed order kinetics (ascorbic acid). Drugs that undergo Michaelis-Menten metabolism are characterized by either increased or decreased metabolism constant (Km) and maximum velocity (Vmax) of enzyme reaction. Hence literatures were searched with a view to translating in vitro-in vivo enzyme kinetics to pharmacokinetic/pharmacodynamic parameters for determination of enzyme inducing and inhibiting drugs, in order to achieve optimal clinical efficacy and safety. Methods A narrative review of retrospective secondary data on drugs, their metabolites, Vmax and Km, generated in the laboratory and clinical environments was adopted, using inclusion and exclusion criteria. Key word search strategy was applied, to assess databases of published articles on enzyme inducing and inhibiting drugs, that obey Michaelis-Menten kinetics. In vitro and in vivo kinetic parameters, such as concentration of substrate, rate of endogenous substrate production, cellular metabolic rate, initial velocity of metabolism, intrinsic clearance, percent saturation and unsaturation of the enzyme substrate, were calculated using original and modified formulas. Years and numbers of searched publications, types of equations and their applications were recorded. Results A total of fifty-six formulas both established and modified were applied in the present study. Findings have shown that theophylline, voriconazole, phenytoin, thiopental, fluorouracil, thyamine and thymidine are enzyme inducers whereas, mibefradil, metronidazole, isoniazid and puromicin are enzyme inhibitors. They are metabolized and eliminated according to Michaelis-Menten principle. The order could be mixed but may change to zero or first order, depending on drug concentration, frequency and route of drug administration. Conclusion Hence, pharmacokinetic-pharmacodynamic translation can be optimally achieved by incorporating, newly modified Michaelis-Menten equations into pharmacokinetic formulas for clinical efficacy and safety of the enzyme inducing and inhibiting therapeutic agents used in laboratory and clinical settings.

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