![]() Therefore the aim of the study is to integrate in vitro kinetics with in vivo kinetics with a view to optimizing clinical efficacy and safety of enzyme inducing and inhibiting drugs. Hence preclinical pharmacokinetic studies remove some drugs out of discovery process. Administration of two or more doses yields better translation. Nonlinear regression algorithms with numerical integration have been used to generate pharmacokinetic parameters. Simple model incorporating Michaelis-Menten type elimination with one compartment model, using intravenous bolus had been published. Hence a minor change in the initial parameter may cause a large change in the final estimates. However, it was assumed that the elimination rate of drug was partly a function of the drug concentration. Michaelis-Menten equation was used to estimate Km and Vmax from initial rate of reaction (V O), at substrate concentration (Cs). Hence analysis of organelle is vital for description of biochemical, molecular and physiological processes that are involved in pathogenesis of diseases, embryogeny, tissue differentiation, aging and treatment of various diseases. Cell organelles involved in metabolism and their dimensions are adiposomes (20 nm–I μm), amphisomes (822 ± 37 nm), apicoplast (0.15–1.5 μm), autophagosome (0.15–1.5 μm), chloroplast (2–10 μm), enlargesome, enosome (30–100 nm), lysosome (0.1–1.2 nm), melanosome ( ≃ 500 nm), mitochondria (0.5–5 μm), nucleus ( ≃ 10 μm), peroxisome (500 nm), phagosome (0.9–3 μm), secretory granule (820 ± 16 μm) and secretory synaptosome (0.5–3 μm). 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.Įlimination half-life, volume of distribution which is responsible for drug transport to sites of metabolism, maximum plasma concentration which could determine metabolism, enzyme saturation and elimination and maximum time (Tmax) reached, may be used to determine time of enzyme saturation, pharmacokinetic and pharmacodynamic response of drugs. The order could be mixed but may change to zero or first order, depending on drug concentration, frequency and route of drug administration. They are metabolized and eliminated according to Michaelis-Menten principle. Findings have shown that theophylline, voriconazole, phenytoin, thiopental, fluorouracil, thyamine and thymidine are enzyme inducers whereas, mibefradil, metronidazole, isoniazid and puromicin are enzyme inhibitors. ResultsĪ total of fifty-six formulas both established and modified were applied in the present study. ![]() Years and numbers of searched publications, types of equations and their applications were recorded. 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. Key word search strategy was applied, to assess databases of published articles on enzyme inducing and inhibiting drugs, that obey Michaelis-Menten kinetics. MethodsĪ 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. 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. Drugs that undergo Michaelis-Menten metabolism are characterized by either increased or decreased metabolism constant (Km) and maximum velocity (Vmax) of enzyme reaction. Some drugs undergo zero-order kinetics (ethyl alcohol), first order kinetics (piroxicam) and mixed order kinetics (ascorbic acid). Pharmacokinetics (PK) is the process of absorption, distribution, metabolism and elimination (ADME) of drugs.
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