Does phenytoin have zero order kinetics?
Phenytoin follows nonlinear (or zero-order) kinetics at therapeutic concentrations, because the rate of metabolism is close to the maximum capacity of the enzymes involved. In nonlinear kinetics, clearance and half-life fluctuate with plasma concentration.
What is saturation kinetics drug?
Drug concentrations in the blood can increase rapidly once an elimination process is saturated. In general, metabolism (biotransformation) and active tubular secretion of drugs by the kidney are the processes most usually saturated. Figure 9-1 shows plasma level–time curves for a drug that exhibits saturable kinetics.
Does phenytoin follow first order kinetics?
Phenytoin metabolism is dose dependent. Elimination follows first-order kinetics (fixed percentage of drug metabolized during a per unit time) at the low drug concentrations and zero-order kinetics (fixed amount of drug metabolized per unit time) at higher drug concentrations.
Does phenytoin have linear kinetics?
As opposed to linear kinetic drugs like vancomycin and aminoglycosides, phenytoin exhibits non-linear kinetics. Meaning a change in dose does NOT produce a proportional change in concentration. It’s also known as zero-order or saturable kinetics because metabolic mechanisms can literally become saturated.
How is phenytoin metabolized?
Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone species that covalently modify proteins.
Which drugs follow first order kinetics?
A few substances are eliminated by zero-order elimination kinetics, because their elimination process is saturated. Examples are Ethanol, Phenytoin, Salicylates, Cisplatin, Fluoxetin, Omeprazol….
| Elimination kinetics | First order | Zero order |
|---|---|---|
| Term in clinical pharmacology | Linear kinetics | Non linear kinetics |
What does saturable mean in pharmacology?
Drug transporters can be saturated if the substrate (drug) levels are sufficiently high. Once the transporter is saturated, no additional drug can be absorbed from the GI tract, even if it is available for transport. Similar to the example of dissolution, increases in the dose will not increase the exposure.
Are most drugs distributed homogeneously?
False Most of drugs are distributed homogeneously.
What drugs are first order kinetics?
Why is phenytoin nonlinear?
The metabolism of phenytoin to the major metabolite, 5-(p-hydroxyphenyl)-5-(phenylhydantoin, is saturable, giving rise to a non linear dose-serum concentration relationship.
How is valproic acid metabolized?
VPA is a fatty acid and can be metabolized through endogenous pathways in the mitochondria (Fig. 1). It has been observed that some of the mitochondrial metabolites of VPA generated by this pathway are hepatotoxic.
Does phenytoin have active metabolites?
All of the commonly used anticonvulsants drugs, except possibly primidone, are cleared from the human body mainly by metabolism. The metabolites of phenytoin, phenobarbital and ethosuximide have so far not been shown to possess significant pharmacological activity.