Half-life, terminal

Pharmacokinetics Rapidly absorbed from the GI tract. Protein binding 95%. Metabolized in the liver. Excreted in urine eliminated in feces. Not removed by hemodialysis. Half-life terminal, 3 hr. 

Trade names Carboplat Carbosin Ercar Oncocarbin Paraplatin (Bristol-Myers Squibb) Paraplatine Indications Various carcinomas and sarcomas Category Alkylating agent Antineoplastic Half-life terminal 22—40 hours... 

Category Colony stimulating factor Erythropoietin Half-life Terminal I.V. = 21 hours... 

Trade names Anexate Lanexat Romazicon (Roche) Indications Benzodiazepine overdose Category Benzodiazepine antagonist Half-life terminal 41-79 minutes... 

Trade names Anamantle HC (Doak) Anestacon Dentipatch DermaFlex Dilocaine ELA-Max (Ferndale) EMLA (AstraZeneca) Lidodan Lidoderm (Endo) Lidoject-2 Octocaine Xylocaine (AstraZeneca) Xylocard Indications Ventricular arrhythmias, topical anesthesia Category Anesthetic, local Antiarrhythmic class I B Half-life terminal 1.5-2 hours... 

Category Antimetabolite Antineoplastic Folate analogue Half-life Terminal up to 198 Hours Clinically important, potentially hazardous interactions with folic acid/folates, L-methylfolate... 

Category Bisphosphonate Half-life terminal 220 hours... 

Because bretylium is poody absorbed from the GI tract (- 10%), it is adrninistered iv or im. Very litde dmg is protein bound in plasma. Bretylium is taken up by an active transport mechanism into and concentrated in postganglionic nerve terminals of adrenergicahy innervated organs. Peak plasma concentrations after im injections occur in about 30 min. Therapeutic plasma concentrations are 0.5—1.0 p.g/mL. Bretylium is not metabolized and >90% of the dose is excreted by the kidneys as unchanged dmg. The plasma half-life is 4—17 h (1,2). 

In a two-compartment model, /3 is equivalent to k in the one-compartment model. Therefore, the terminal half-life for the elimination of a chemical compound following two-compartment model elimination can be calculated from the equation (i = 0.693/ti/i ... 

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Proteins with destabilizing N-terminal residues such as arginine and leucine are recognized by a RING-type ubiquitin ligase (termed N-recognin or E3-a) that, together with a specific ubiquitin c, mediates poly-ubiquitylation. 

Half-life is the time taken to decrease the concentration of a drug to one-half its original value. There may be several phases in the elimination, and the most common is the so-called beta-phase. Alpha-phase is a distribution phase and gamma-phase is the terminal phase when the drug is finally leaving the tissues. 

Pharmacokinetic studies demonstrated good oral bioavailability of maraviroc and a terminal half-life of 16-23 h following multiple dosing (Abel et al. 2003 Walker et al. 2005). Single doses of up to 900 mg and multiple doses of up to 300 mg BID for 28 days were well tolerated (Abel et al. 2003 Russell et al. 2003 Walker et al. 2005). In Phase 2a studies, treatment-naive HIV-1 patients with R5 virus who received maraviroc monotherapy at doses ranging from 25 mg QD to 300 mg BID for 10 days experienced a median viral load reduction of 1.64 log jg copies/mL and... 

The unbound PCP concentration was calculated by multiplying the total unchanged PCP concentration In serum by the unbound fraction in serum at each time point. The harmonic means for the terminal elimination half-life for unchanged total PCP and unbound PCP were virtually the same (3.5 and 3.3 hours, respectively). The arrows indicate the time of Fab administration. 

The area under the PCP concentration-time curve (AUC) from the time of antibody administration to the last measured concentration (Cn) was determined by the trapezoidal rule. The remaining area from Cn to time infinity was calculated by dividing Cn by the terminal elimination rate constant. By using dose, AUC, and the terminal elimination rate constant, we were able to calculate the terminal elimination half-life, systemic clearance, and the volume of distribution. Renal clearance was determined from the total amount of PCP appearing in the urine, divided by AUC. Unbound clearances were calculated based on unbound concentrations of PCP. The control values are from studies performed in our laboratory on dogs administered similar radioactive doses (i.e., 2.4 to 6.5 pg of PCP) (Woodworth et al., in press). Only one of the dogs (dog C) was used in both studies. 

Azacitidine, a cytidine analog, causes hypomethylation of DNA, which normalizes the function of genes that control cell differentiation to promote normal cell maturation. The suspension is administered as a subcutaneous injection daily for 7 days for the treatment of myelodysplastic syndrome, a preleukemia disease. The pharmacokinetics of azacitidine are best described by a two-compartment model, with a terminal half life of 3.4 to 6.2 hours, whereas peak concentrations are achieved 30 minutes after a subcutaneous injection.7 Azacitidine has been shown to be clinically active in the treatment of myelodysplastic syndromes. The side effects include myelosuppression, renal tubular acidosis, renal dysfunction, and injection-site reactions. 

Vinblastine is another vesicant vinca alkaloid that causes myelo-suppression and less neurotoxicity than vincristine. The pharmacokinetics of vinblastine are best described by a three-compartment model, with an a half-life of 25 minutes, a 3 half-life of 53 minutes, and a terminal half-life of 19 to 25 hours.12 Vinblastine has shown activity in the treatment of bladder, breast, and kidney cancer, as well as some lymphomas. The doses of vinblastine tend to be higher on a milligram per meter squared basis than vincristine. Nausea and vomiting are minimal with vinblastine. Other side effects include mild alopecia, rash, photosensitivity, and stomatitis. 

Docetaxel, another taxane, binds to tubulin to promote microtubule assembly. The pharmacokinetics of docetaxel are best described by a three-compartment model, with an a half-life of 0.08 hours, a 3 half-life of 1.6 to 1.8 hours, and a terminal half-life of 65 to 73 hours.14 Docetaxel has activity in the treatment of breast, non-small cell lung, prostate, bladder, esophageal, stomach, ovary, and head and neck cancers. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid... 

Estramustine, an oral drug, also inhibits microtubule assembly and has weak estrogenic activity at the estradiol hormone receptors of the cell. Approximately 75% of a dose of estramustine is absorbed.15 The terminal half-life ranges between 20 to 24 hours, with nonrenal excretion as the major route of elimination. This drug is used primarily for the treatment of prostate cancer, but its use is limited by the side effects, which include nausea and vomiting, diarrhea, thromboembolic events, and gynecomastia. 

Teniposide, a topoisomerase II inhibitor, is administered as an infusion over 30 to 60 minutes to prevent hypotension. The pharmacokinetics are described by a three-compartment model, with an a half-life of 0.75 hours, a (5 half-life of 4 hours, and a terminal half-life of 20 hours. Considerable variability in clearance of teniposide in children has been reported.17 Teniposide has shown activity in the treatment of acute lymphocytic leukemia, neuroblastoma, and non-Hodgkin s lymphoma. Side effects include myelosuppression, nausea, vomiting, mucositis, and venous irritation. Hypersensitivity reactions may be life-threatening. 

Topotecan inhibits topoisomerase I to cause single-strand breaks in DNA. The pharmacokinetics of topotecan can be described by a two-compartment model, with a terminal half-life of 80 to 180 minutes, with renal clearance accounting for approximately 70% of the clearance.19 Topotecan has shown clinical activity in the treatment of ovarian and lung cancer, myelodysplastic syndromes, and acute myelogenous leukemia. The intravenous infusion may be daily for 5 days or once weekly. Side effects include myelosuppression, mucositis, and diarrhea. 

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