Plasma elimination, pharmacokinetic

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 Rapidly and extensively absorbed after PO administration. Protein binding 20%-25%. Rapidly metabolized to penciclovir by enzymes in theGI wall, liver, and plasma. Eliminated unchanged in urine. Removed by hemodialysis. Half-life 2 hr. 

Mechanism of Action A tissue plasminogen activator that activates the fibrinolytic system by directly cleaving plasminogen to generate plasmin, an enzyme that degrades the fibrin ot the thrombus. Therapeutic Effect Exerts CV-thrombolytic action. Pharmacokinetics Rapidlycleared from plasma. Eliminated primarilyby the liverand kidney. Haif-Hfe 13-16 min. 

Pharmacokinetics According to the product label, the pharmacokinetics of eptihbatide are linear and dose proportional. Plasma elimination half-life is approximately 2.5 hours. The extent of eptihbatide binding to human plasma protein is about 25% its mean volume of distribution is 185mPkg. Clearance in patients with coronary artery disease is 55-58 ml/kg per hour. Clinical studies have included 2418 patients with serum creatinine between 1.0 and 2.0mg/dl without dose adjustment. No data are available in patients with more severe degrees of renal impairment, but plasma eptihbatide levels are expected to be higher in such patients. Patients in clinical studies were older than the subjects in clinical pharmacology studies, and they had lower total body eptihbatide clearance and higher eptihbatide plasma levels. Men and women showed no important differences in the pharmacokinetics of eptihbatide. 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Pharmacokinetic studies in mice, rats, and dogs showed that cephapirin was readily metabolized into desacetylcephapirin. The rate and the extent of this metabolism showed a decreasing tendency from rodents to dogs. In these species, the plasma elimination half-lives of cephapirin and desacetylcephapirin were 0.4-0.9 h. In dairy cows, cephapirin was mainly eliminated by the urinary route and, to a smaller extent, by the biliary route. 

Pharmacokinetic studies in heifers showed that plasma peak levels of norgestomet were reached within 2-6 h after dosing. Plasma elimination half-lives were estimated at 4.3-9.5 days after removal of the implant. Elimination occurred mainly via feces within 18 days after treatment. 

The pharmacokinetic profile of 2 -MOE partially modified ASOs was similar in mice, rats, dogs, monkeys, and humans in that the drug was cleared within hours from the plasma and distributed to the tissues. Following IV administration, the plasma concentration-time profiles of 2 -MOE partially modified ASO are poly-phasic, characterized by a rapid distribution phase (half-lives of 30-80 min), followed by at least one additional much slower elimination phase with half-lives reported from 10 to 30 days. The recent development of ultrasensitive hybridization ELISA methods have made it possible to follow plasma concentrations for up to three months after dose administration, enabling the investigators to determine terminal plasma elimination half-lives [24, 26, 30, 31]. Representative plasma concentration-time profiles with the rapid distribution phase along the slow terminal elimination phase in monkeys and humans for a 2 -MOE partially modified ASO, ISIS 104838 are shown in Figure 4.2 [26]. 

Pharmacokinetic studies in several animal species (seeTttble 3) have shown that nongiycosyiated recombinant ai-FI has a much shorter piasma half-life than the native form of ai-PI (1-2 hours vs. 2-4 days) [61,62]. Since the proposed mode of delivery of ai-PI is by aerosolization, rapid plasma elimination should not be a concern. It has been demonstrated that both recombinant and native... 

Example Reteplase, recombinant Route IC Pregnancy category C Pharmacokinetic Rapidly cleared from plasma eliminated by the liver and kidney. 

The metabolic disposition and clinical pharmacokinetics of clofibrate have been recently reviewed. In healthy volunteers, the plasma elimination half-life (tj) of chlorophenoxyisobutyrlc acid (CPIB), the pharmacologically active form of clofibrate, averaged 17 hr, independent... 

Pharmacokinetic studies in several animal species (see Table 3) have shown that nonglycosylated recombinant ai-PI has a much shorter plasma half-life than the native form of ai-PI (1-2 hours vs. 2-4 days) [61,62]. Since the proposed mode of delivery of ai-PI is by aerosolization, rapid plasma elimination should not be a concern. It has been demonstrated that both recombinant and native at-PI can be aerosolized without loss of inhibitory activity and animal studies have shown that aerosolized at-PI has an extended lung half-life. We have also investigated the pharmacokinetics of recombinant ai-PI in rat. The distribution and elimination half-life after bolus intravenous application of 2 mg/kg were approximately 25 and 100 minutes, respectively. After intratracheal application of recombinant ai-PI, plasma levels peaked between 4 and 8 hours after administration, and the half-life of disappearance from the lung was approximately 12.5 hours as measured by ELISA and 11 hours as determined by antielastase activity. This confirms that ai-PI administered to the lung remains active for an extended period of time and is able to cross from the lung into the blood. Low amounts of... 

Because IFNs induce long-lasting cellular effects, their activities are poorly predicted from usual pharmacokinetic measures. After intravenous dosing, clearance of IFN from plasma occurs in a complex manner. With subcutaneous or intramuscular dosing, the plasma elimination t of IFN-a ranges from 3 to 8 hours, largely due to distribution to the tissues, cellular uptake, and catabolism in the kidney and liver. Negligible amounts are excreted in the urine. Clearance of IFN-a is reduced by 7Wc in dialysis patients. 

Ifosfamide has a plasma elimination t of 15 hours after doses of 3.8-5 g/rrf and a somewhat shorter t at lower doses, although its pharmacokinetics are highly variable due to variable rates... 

Figure 15.3 The relationship between plasma concentration (Cp) and time following the administration of different doses of a drug that exhibits dose-dependent elimination pharmacokinetics.

In contrast to the naturally occurring Gd compounds, pharmacokinetic and pharmacological properties of the element s DOTA and DTPA chelates that are used in MRl have been studied more intensively. From a kinetic point of view, these highly hydrophilic compounds behave in an identical fashion. As expected from hydrophilic substances, the volume of distribution is small being 0.17 0.01 liters/kg in humans [13] while the plasma elimination half-life is around 20 and 90 min in rats and humans, respectively [4]. In mice 89% of the administered Gd-DOTA and Gd-DTPA doses was recovered in the urine within 1 hr [14]. In correlation with the reduced GFR in patients with chronic renal failure (median creatinine clearance 25.5 mL/min) the serum half-life of Gd-DTPA was prolonged and the renal clearance decreased. Recovery of the Gd-DTPA after administration of a 0.1 mmol/kg dose was 92 12%, whereas extrarenal elimination in these subjects accounted for less than 0.4% [15], indicating that glomerular filtration is the predominant route of elimination of the chelates. 

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). 

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). 

The realization of sensitive bioanalytical methods for measuring dmg and metaboUte concentrations in plasma and other biological fluids (see Automatic INSTRUMENTATION BlosENSORs) and the development of biocompatible polymers that can be tailor made with a wide range of predictable physical properties (see Prosthetic and biomedical devices) have revolutionized the development of pharmaceuticals (qv). Such bioanalytical techniques permit the characterization of pharmacokinetics, ie, the fate of a dmg in the plasma and body as a function of time. The pharmacokinetics of a dmg encompass absorption from the physiological site, distribution to the various compartments of the body, metaboHsm (if any), and excretion from the body (ADME). Clearance is the rate of removal of a dmg from the body and is the sum of all rates of clearance including metaboHsm, elimination, and excretion. 

The pharmacokinetics of azacitidine shows that it is rapidly absorbed after s.c. administration with the peak plasma concentration occurring after 0.5 h. The bioavailability of s.c. azacitidine relative to i.v. azacitidine is approximately 89%. Urinary excretion is the primary route of elimination of azacitidine and its metabolites. The mean elimination half-lives are about 4 h, regardless of i.v. or s.c. administration. 

In practice, one will seek to obtain an estimate of the elimination constant kp and the plasma volume of distribution Vp by means of a single intravenous injection. These pharmacokinetic parameters are then used in the determination of the required dose D in the reservoir and the input rate constant k (i.e. the drip rate or the pump flow) in order to obtain an optimal steady state plasma concentration... 

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. 

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