Distribution half-life

Transfer constant of absorption Plasma volume of distribution Half-life time, a-phase ... 

The half-life (fi/2) of a drug is a function of two variables clearance and volume of distribution. Half-life is directly related to volume of distribution (VD) and inversely related to clearance (CL) ... 

Areas under the curves, volume of distribution, half-life Metablic pattern of test article Distribution to key organs... 

Also included in in vivo data is a set of human (90% of drugs) and animal pharmacokinetic (30% of drugs) data. While the in vitro data are generated in-house (Cerep), pharmacokinetic data are gathered from the literature. A variety of different parameters are covered including absolute bioavailability, oral absorption, clearance, volume of distribution, half-life, protein binding and excretion information. 

Absorption - Darbepoetin has an approximately 3-fold longer terminal half-life than epoetin alfa when administered by either the IV or subcutaneous route. Following IV administration, darbepoetin has a distribution half-life of approximately 1.4 hours and mean terminal half-life of approximately 21 hours. 

The duration and degree of reversal of benzodiazepine effects are related to the dose and plasma concentrations of flumazenil. The onset of reversal is usually evident within 1 to 2 minutes after the injection is completed. Within 3 minutes, 80% response will be reached, with the peak effect occurring at 6 to 10 minutes. Pharmacokinetics After IV administration, flumazenil has an initial distribution half-life of 7 to 15 minutes and a terminal half-life of 41 to 79 minutes. Peak concentrations of flumazenil are proportional to dose, with an apparent initial volume of distribution of 0.5 L/kg. After redistribution the apparent volume of distribution ranges from 0.77 to 1.6 L/kg. Protein binding is approximately 50%. 

Pharmacokinetics Well absorbed from GI tract. Protein binding 23% -33%. Widely distributed. Half-life 18-24 hr. 

Because BZs are redistributed until over 95% of the drug is outside the blood circulation and the brain, it is the distribution half-life that is most important in determining the duration of action of each BZ. Unfortunately, it is the elimination half-life that is most studied and best known (see Table 27.1 Chouinard et ah, 1999). 

Pharmacokinetics The volume of distribution of filgrastim averages 150mFkg. Its distribution half-life is 30 minutes, and its elimination half-life is 3 to 4 hours with a clearance of 0.5 to O.TmFmin per kilogram. 

Pharmacokinetics Aldesleukin displays biphasic pharmacokinetics, with an alpha (distribution) half-life of 13 minutes and a beta (terminal) half-life of 85 minutes. In cancer patients, the mean clearance rate of aldesleukin is 268 ml/min. 

Pharmacokinetics The absorption rate of Gonal-F following subcutaneous or intramuscular administration was found to be slower than the elimination rate. Hence the pharmacokinetics of Gonal-F are absorption rate-limited. After intravenous administration to pituitary down-regulated, healthy female volunteers, the serum profile of FSH appears to be described by a two-compartment open model with a distribution half-life of about 2 to 2.5 hours. Steady-state serum levels were reached after 4 to 5 days of daily administration. 

Volume of Distribution Half-life Effective Dose Toxic Dose Major Route of Elimination... 

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... 

In rats receiving [ Cjbenzyl chloride in corn oil by gavage, the peak plasma level was reached after 30 min. The distribution half-life was 1.3 h, while the elimination half-life was 58.5 h. After 48 h, the higher concentrations were found in the stomach, gastric contents, ileum and duodenum, followed by liver, adrenal, bone marrow and blood. After 72 h, approximately 76% was excreted in urine and, in expired air, 7% as 002 and less than 1.3% as benzyl chloride or its metabolites. Urinary metabolites were identified as Y-benzyl-A-acetyl cysteine, benzx l alcohol and benzaldehyde (Saxena Abdel-Rahman, 1989). 

The pharmacokinetics fCD and HlftCD after intravenous administration have been assessed (Frijlinket al., 1990). As determined at doses of 25,100, and 200 mg/kg in permanently cannulated rats, plasma levels of both CDs decreased rapidly upon injection. Within 24 h after administration, most of the doses were excreted unchanged via urine. There was no evidence forsigniLcant metabolism of the intravenously administered CDs. The pharmacokinetics and the tissue concentrations of methyl-p-cyclodextrin (MEBCD) and doxorubicin (DOX) in rabbits following administration of MEBCD and DOX, alone or in combination were studied (Grosse et al., 1999). Results indicated that DOX did not modify MEBCD pharmacokinetic proLle, but MEBCD reduced signiLcantly the distribution half-life of DOX. Tissue determination showed that MEBCD did not enhanced the cardiac accumulation of DOX. 

Cl plasma concentration at time zero fi/2a, distribution half-life f1/2jg, elimination half-life Kej, elimination rate constant from central compartment Ki2/.K2i, transfer rate constant between peripheral and central compartments AUC(o ), total area under plasma drug concentration time curve Vd(area> apparent volume of distribution GB, total body clearance. 

GHRH is not currently available commercially in research use it may be administered intravenously, subcutaneously, or intranasally, and the relative potencies (defined as incremental growth hormone release) by these three routes are 300, 10, and 1, respectively. Intravenous GHRH (1 g/kg) has a distribution half-life of 4 minutes and an elimination half-life of 53 minutes. Subcutaneous GHRH has a similar elimination half-life but a distribution half-life of about 10 minutes. Peak serum levels of GHRH (1 g/kg) are 37 times higher after intravenous administration compared with subcutaneous injection. Sermorelin, 2 g/kg subcutaneously, reaches peak serum concentrations in 5-20 minutes its bioavailability is 6%. The half-life of sermorelin is about 12 minutes after either subcutaneous or intravenous injection. 

A plasma concentration-time profile that is poly-phasic with rapid distribution half-life (< 1 h) and long elimination half-life reflecting slow elimination from the tissues. 

Cmax = peak plasma concentration rl/2c, = distribution half-life /l2 i = elimination half-life AUC = area under the plasma concentration-time curve Cl = total body clearance Fd = volume of distribution. Values shown are mean SD (n = 2). 

In the clinic, esmolol s distribution half-life is 2 min and its elimination half-life is 9 min. Esmolol hydrochloride is rapidly metabolized by hydrolysis of the ester linkage, chiefly by esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase [22]. Its volume of distribution is 3.4 L kg-1, and its total clearance is 285 mL kg-1 min-1, "... which is greater than cardiac output thus the metabolism ofesmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flout [22]. As expected from such a "... high rate of blood-based metabolism, less than 2% of the drug is excreted unchanged in the wind [22]. Within 24 h after infusion, approximately... 

A brief description of the pharmacokinetic characteristics of the active ingredient(s) and the performance of the dosage form, integrating conclusions from the bioavailability and pharmacokinetic studies and from clinical studies performed. Information on volume of distribution, half-life, routes and rates of excretion, and metabolism of each dosage form studies, and the proportionality of absorption over the therapeutic dose range should be included. If pertinent, a comparison with the bioavailability of other dosage forms should be provided. 

---