Half-life drug distribution effects

Currently, eleven ACE inhibitors are available for clinical use in the United States. In general, they differ among themselves with regard to three properties (1) potency, (2) whether ACE inhibition is primarily a direct effect of the drug itself or the effect of an active metabolite, and (3) pharmacokinetics (i.e., extent of absorption, effect of food on absorption, plasma half-life, tissue distribution, and mechanisms of elimination). 

Although these divisions are of historical interest, duration of action, especially with a single dose, depends more on distribution effects than on elimination half-life. Furthermore, as the dose increases, duration of action is prolonged. In addition, the availability of these drugs in the United States is limited. 

Oxcarbazepine Modulate sodium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 600-1200 mg/day. Start at 300 mg twice daily and titrate upward as indicated by response Half-life Not established Parent drug 2 hours 1 0-monohydroxy metabolite 9 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding 40% Primary elimination route Hepatic Diplopia, dizziness, somnolence Hyponatremia, 25-30% cross sensitivity in patients with hypersensitivity to carbamazepine... 

The units of volume of distribution are those of volume (i.e. litres) and can be adjusted for, say, body weight. The two main uses of volume of distribution are in the calculation of loading doses for rapid onset of drug effect, and in understanding changes in half-life (see below). 

Combinations of amphotericin-B with flucytosine are sometimes used to reduce the occurrence of resistance. Amphotericin-B is not absorbed from the gastrointestinal tract which necessitates intravenous administration. It is 90% protein bound and widely distributed, except for the CNS. For the treatment of fungal meningitis therefore only intrathecal drug administrations can be effective. Amphotericin-B is eliminated very slowly in urine, mainly in an inactive form, with an elimination half-life of about 24 hours which can increase to up to 15 days with repeated doses. 

These results indicate that, in addition to effectiveness by inhalation and parenteral administration, SNA is well absorbed in man when administered orally. The drug is 60-70% bound to plasma proteins, the volume of distribution is high (approximately 500 L In an 80-kg man), clearance is largely a result of metabolic processes, the half-life Is quite variable from one person to another, and the drug and its metabolites are excreted principally in the urine, regardless of whether it is given orally or intravenously. 

Category Drug Name TTade Name Dosage Form and Dose Route of Administration Clearance Volume of Distribution Half-life Effective Dose Toxic Dose Major Route of Elimination... 

This agent has a broad spectrum of activity encompassing several neurotransmitter systems. In this light, clozapine is similar to such phenothiazines as CPZ and thioridazine (519). It is also subject to a hepatic first-pass effect, which produces metabolites with low or unknown pharmacological activity. It has an elimination half-life ranging from 6 to 33 hours and a volume of distribution (V 5 l /kg) lower than most other antipsychotics. This last quality indicates less drug is sequestered in tissue sites. Plasma levels of the parent compound at or above 350 ng/mL may be associated with a better clinical response ( 66, 520). Plasma levels are lower in men than women, especially male smokers (329). 

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