Pharmacokinetics elimination half-life

Medroxyprog esteroneAcetate. Accurate pharmacokinetic and metaboHsm studies on MPA have been difficult because the radioimmunoassays employed caimot differentiate between MPA and its metaboHtes (346). Comparison of MPA plasma levels assayed by hplc and radioimmunoassay show that radioimmunoassay may overestimate intact MPA concentrations by about fivefold (347). However, values of the mean elimination half-life of MPA were similar, being 33.8 and 39.7 h when measured by hplc and radioimmunoassay, respectively (347). Approximately 94% of MPA in the blood is bound to albumin (348). When taken orally, MPA is rapidly absorbed with Htde or no first-pass metaboHsm (13). Peak semm levels ate reached after 3 h. Steady state occurs after three days of daily adininistration (349). The pharmacokinetics of MPA when adininistered in a depot formulation have been described (350). 

Elestolol sulfate is a nonselective, ultrashort acting P-adrenoceptor blocker. It has no ISA and produces weak inhibition of the fast sodium channel. The dmg is under clinical investigation for supraventricular tachyarrhythmias, unstable angina, and acute MI. In humans, flestolol has hemodynamics and electrophysiologic effects similar to those of other P-adrenoceptor blockers. The pharmacokinetics of flestolol are similar to those of esmolol. It is 50 times more potent than esmolol and the elimination half-life is 7.2 min. Recovery from P-adrenoceptor blockade is 30—45 min after stopping iv infusions. The dmg is hydrolyzed by tissue esterases and no active metabohtes of flestolol have been identified (41). 

Bopindolol is a long-acting, nonselective P-adrenoceptor blocker. It has mild membrane stabilizing activity and ISA. In vivo, the compound is hydrolyzed to its active metabohte. Because of this prodmg feature the onset of action is slower than other available P-adrenoceptor blockers. Preliminary pharmacokinetic studies indicate that the compound is weU absorbed, is 70% bioavailable, and peak plasma levels are achieved in about 2 h. Whereas its elimination half-life is 4—8 h, P-adrenoceptor blocking action (- 40%) is stiU apparent after 48 h. The dmg is being studied in hypertension, angina, and arrhythmias (43). 

Half-life /Elimination Half-life Pharmacokinetics... 

Anastrozole is a selective nonsteroidal aromatase inhibitor that lowers estrogen levels. The pharmacokinetics of anastrozole demonstrate good absorption, with hepatic metabolism the primary route of elimination and only 10% excreted unchanged by the kidney. The elimination half-life is approximately 50 hours. Anastrozole is used for the adjuvant treatment of postmenopausal women with hormone-positive breast cancer and in breast cancer patients who have had disease progression following tamoxifen. Side effects include hot flashes, arthralgias, osteoporosis/bone fractures, and thrombophlebitis. 

Toremifene is an estrogen receptor antagonist. The pharmacokinetics of toremifene are best described by a two-compartment model, with an a half-life of 4 hours and an elimination half-life of 5 days. Peak plasma concentrations are achieved approximately 3 hours after an oral dose. Toremifene is metabolized extensively, with metabolites found primarily in the feces. Toremifene is used for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor-positive or unknown tumors. Toremifene causes hot flashes, vaginal bleeding, thromboembolism, and visual acuity changes. 

Daneshmend [104] measured the serum concentration of miconazole in 11 healthy adult females for 72 h following a single 1200 mg vaginal pessary. The mean peak serum miconazole concentration was 10.4 pg/L and the mean elimination half-life was 56.8 h. The mean area under the serum concentration-time curve was 967 pg/L/h. The calculated mean systemic bioavailability of the vaginal pessary was 1.4%. There was large intersubject variation in serum miconazole pharmacokinetics. This formulation may provide effective single dose treatment for vaginal candidiasis. 

From 10 to 20% of an oral dose of miconazole is excreted in the urine, mainly as metabolites, within 6 days. About 50% of an oral dose may be excreted mainly unchanged in the feces. The elimination pharmacokinetics of miconazole have been described as triphasic, with a biological half-life of about 24 h. With an initial half-life of about 0.4 h, and intermediate half-life of about 2.5 h and elimination half-life of 24 h. Very little miconazole is removed by haemodialysis [3]. 

Ward et al. [125] investigated the disposition of 14C-radiolabeled primaquine in the isolated perfused rat liver preparation, after the administration of 0.5, 1.5, and 5 mg doses of the drug. The pharmacokinetics of primaquine in the experimental model was dependent on dose size. Increasing the dose from 0.5 to 5 mg produced a significant reduction in clearance from 11.6 to 2.9 mL/min. This decrease was accompanied by a disproportionate increase in the value of the area under the curve from 25.4 to 1128.6 pg/mL, elimination half-life from 33.2 to 413 min, and volume of distribution from 547.7 to 1489 mL. Primaquine exhibited dose dependency in its pattern of metabolism. While the carboxylic acid derivative of primaquine was not detected perfusate after the 0.5 mg dose, it was the principal perfusate metabolite after 5 mg dose. Primaquine was subject to extensive biliary excretion at all doses, the total amount of 14C-radioactivity excreted in the bile decreased from 60 to 30%i as the dose of primaquine was increased from 0.5 to 5 mg. 

Mihaly et al. [127] examined the pharmacokinetics of primaquine in healthy volunteers who received single oral doses of 15, 30, and 45 mg of the drug, on separate occasions. Each subject received an intravenous tracer dose of 14C-prima-quine (7.5 pCi), simultaneously with 45 mg oral dose. Absorption of primaquine was virtually complete with a mean absorption bioavailability of 0.96. Elimination half-life, oral clearance, and apparent volume of distribution for both primaquine and the carboxylic acid metabolite were unaffected by either dose size or route of administration. 

Yoshimura et al. [132] studied the pharmacokinetics of primaquine in calves of 180—300 kg live weight. The drug was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously or subcutaneously and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high performance liquid chromatography. The extrapolated concentration of primaquine at zero time after the intravenous administration was 0.5 0.48 pg/mL which decreased with an elimination half-life of 0.16 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.5 0.08 pg/mL at 1.67 0.15 h after intravenous administration. The corresponding value was 0.47 0.07 pg/mL at 5.05 1.2 h after subcutaneous administration. The elimination half-lives of carboxyprimaquine after intravenous and subcutaneous administration were 15.06 0.99 h and 12.26 3.6 h, respectively. 

Product pharmacokinetics were evaluated in healthy volunteers and a single s.c. injection (60 pg) resulted in a peak serum concentration Cmax = 5.1 IU ml with a median time of peak serum concentration Tmax = 16 h. The serum elimination half-life t1/2 was of the order of 70 h. 

An increase in the elimination half-life in rats was achieved by blocking the benzylic position of the propionic acid chain by introduction of a cyclopropane ring 22 (%F = 88, Vdss = 1 L/kg, f1/2 = 6.3 h) however, in the case of 22, this led to a reduction in the receptor subtype selectivity (EC50 on SI Pi/1,5 = 0.21,123 and 5.1 nM, respectively). Similarly, blocking the benzylic position by cyclizing onto the phenyl ring to form indanylacetic acid 23 resulted in an improved elimination of half-life (%F — 71, Vdss = 0.4L/kg, f1/2 = 6.7h). Acid 23 showed a similar pharmacokinetic profile in the dog and showed efficacy in the rat skin transplantation model when combined with sub-therapeutic doses of CsA. Compound 23 has been reported to be efficacious in the rat EAE model when dosed therapeutically or prophylactically [94—96]. 

Caffeine pharmacokinetics are nonlinear. For example, when comparing a 500 mg dose to a 250 mg dose, the clearance is reduced and elimination half-life is prolonged with the higher dose (Kaplan et al. 1997). Thus, larger doses prolong the action of the drug. Active metabolites of caffeine are paraxanthine, and to a lesser degree, theobromine, and theophylline. Urinary metabolites are I-methylxanthine, l-methyluric acid, and an acetylated uracil derivative. 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

There is substantial variability in the pharmacokinetics of vinblastine in patients. Evidence has been obtained that implicates altered liver function and dose-dependent elimination as contributing factors to the variable pharmacokinetics. When vinblastine was administered by a bolus injection, a mean terminal elimination half-life of 29.2 hr was estimated for a group of 24 patients, but the half-lives ranged from a low value of 16 hr to a high value of 65 hr (55). When vinblastine was administered by intravenous infusion, clearance of the drug appeared to decrease with time over a 4-month period decreases in serum albumin values were found to be correlated with decreases in the clearance of vinblastine. 

Reanalysis of the data of Hattis et al. (1987) showed that the variation between individuals for the elimination half-life was quite small (Schaddelee 1997, as cited in Vermeire et al. 1999, 2001). Defining the interindividual factor as the ratio of the P50 (50th percentile) and P05 (5th percentile) resulted in a factor of 1.4. It was emphasized that although it appeared from this analysis that a 10-fold factor would be sufficient for pharmacokinetic variation, the real median to sensitive human variability is underestimated because variation also exists in pharmacodynamics and only data of healthy volunteers were available. 

Pharmacokinetics Niacin is rapidly absorbed from the Gl tract peak serum concentrations usually occur within 45 minutes. The plasma elimination half-life is approximately 45 minutes. Approximately one third of an oral dose is excreted unchanged in the urine. 

Pharmacokinetics In healthy adults treated with IV doses of iron sucrose, its iron component exhibits first order kinetics with an elimination half-life of 6 hours, total clearance of 1.2 L/h, non-steady-state apparent volume of distribution of 10 L, and steady-state apparent volume of distribution of 7.9 L. 

Pharmacology Succimer is an orally active, heavy metal chelating agent it forms water soluble chelates and, consequently, increases the urinary excretion of lead. Pharmacokinetics In a study in healthy adult volunteers, after a single dose of 16, 32, or 48 mg/kg, absorption was rapid but variable, with peak blood levels between 1 and 2 hours. Approximately 49% of the dose was excreted 39% in the feces, 9% in the urine, and 1 % as carbon dioxide from the lungs. Because fecal excretion probably represented nonabsorbed drug, most of the absorbed drug was excreted by the kidneys. The apparent elimination half-life was about 2 days. 

Metabolism/Excretion - There are 2 genetically determined patterns of propafenone metabolism. In more than 90% of patients, the drug is rapidly and extensively metabolized with an elimination half-life of 2 to 10 hours. These patients metabolize propafenone into two active metabolites 5-hydroxypropafenone and N-depropylpropafenone. They both are usually present in concentrations less than 20% of propafenone. The saturable hydroxylation pathway is responsible for the nonlinear pharmacokinetic disposition. 

Excretion - The terminal elimination half-life is between 5 and 6 days following inhalation. After dry powder inhalation, urinary excretion is 14% of the dose, the remainder being mainly nonabsorbed drug in the gut, which is eliminated via the feces. The renal clearance of tiotropium exceeds the Ccr, indicating active secretion into the urine. After chronic, once-daily inhalation by COPD patients, pharmacokinetic steady state was reached after 2 to 3 weeks with no accumulation thereafter. 

Pharmacokinetics Oral zafirlukast is rapidly absorbed. Peak plasma concentrations are achieved 3 hours after dosing. The mean terminal elimination half-life is about 10 hours. Zafirlukast is more than 99% bound to plasma proteins, predominantly albumin. 

Amphetamine mixture - Peak plasma concentrations occur in about 3 hours (Adderall) and 7 hours (Adderall XR). Elimination half-life is 10 to 13 hours in adults and 9 to 11 hours in children. Extended-release amphetamine mixture capsules demonstrate linear pharmacokinetics. There is no unexpected accumulation at steady state. Food does not affect the extent of absorption of extended-release amphetamine mixture capsules, but prolongs T ax by 2.5 hours. 

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