Terminal elimination half-life

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. 

When khat is chewed, absorption of cathinone is slow, with maximal plasma concentrations occurring at approximately 2 hours (Widler et al. 1994 Halket et al. 1995). The terminal elimination half-life is approximately 4.3 hours. Similar effects are achieved with orally administered pure cathinone. Cathinone is the keto-analog of cathine and because it is more lipophilic it penetrates the blood-brain barrier more easily. 

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. 

Metaboiism/Excretion-The terminal elimination half-life for drug bound iron was approximately 1 hour, varying by dose but not by rate of administration. Total clearance was 3.02 to 5.35 L/h. In vitro, less than 1 % of the iron species within sodium ferric gluconate complex can be dialyzed through membranes with pore sizes corresponding to 12,000 to 14,000 daltons over a period of up to 270 minutes. 

Excretion - Total body clearance is about 5.1 mL/min/kg (0.31 L/h/kg) for infusion doses 40 mcg/kg/min or less. The terminal elimination half-life of argatroban ranges between 39 and 51 minutes. Argatroban is excreted... 

The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. The average steady-state serum dutasteride concentration was 40 ng/mL following 0.5 mg/day for 1 year. 

Excretion - After IV administration of 1 mg to healthy males, plasma concentrations declined biexponentially with a redistribution and a terminal elimination half-life of 41 34 minutes and 10.8 5.2 hours, respectively. The systemic clearance of nalmefene is 0.8 L/h/kg and the renal clearance is 0.08 L/h/kg. 

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. 

Pharmacokinetics The elimination half-lives of these drugs range from 4 to 8 hours. Elimination is primarily via hepatic metabolism. Plasma concentrations of alosetron are 30% to 50% lower and less variable in men compared with women given the same dose. Plasma protein binding is 82% for alosetron, 65% for granisetron and 70% to 76% for ondansetron. The terminal elimination half-life of alosetron is approximately 1.5 hours. 

Metabolism/Excretion- Memantine undergoes little metabolism, with the majority (57% to 82%) of an administered dose excreted unchanged in urine. Memantine has a terminal elimination half-life of about 60 to 80 hours. Renal clearance involves active tubular secretion. 

Metabolism/Excretion— Miconazole is rapidly metabolized in the liver. About 14% to 22% of the administered dose is excreted in the urine, mainly as inactive metabolites. The terminal elimination half-life is 20 to 25 hours. 

Metabolism/Excretion-The terminal elimination half-life is approximately 128 to 149 hours. 

Metabolism/Excretion - Following a single oral dose of tenofovir, the terminal elimination half-life is approximately 17 hours. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. 

The plasma protein binding of tacrolimus is approximately 99%. Tacrolimus is bound mainly to albumin and alpha-1-acid glycoprotein and has a high level of association with erythrocytes. It is extensively metabolized by the mixed-function oxidase system, primarily the cytochrome P450 system (CYP3A). The disposition of tacrolimus from whole blood was biphasic with a terminal elimination half-life of 11.7 hours in liver transplant patients. 

L, volume of peripheral compartment is 3.4 L. The estimated terminal elimination half-life for the reference patient was 20 days (480 hours), which is similar to the terminal elimination half-life for human IgG (18 to 23 days). Bayesian estimates of terminal elimination half-life ranged from 11 to 38 days for the 123 patients included in the population analysis. 

Mean serum clearance values ranged from 9.4 to 28.9 mL/min/kg and were independent of dose. Mean terminal elimination half-life values ranged from 8 minutes to 4.3 hours and mean steady-state volume of distribution values ranged from 0.25 to 2.88 L/kg. IV dosing 3 times/week for 2 weeks resulted in no accumulation of interferon beta-la or beta-lb in the serum of patients. 

Irinotecan has demonstrated a broad spectrum of activity in vitro and in vivo, and synergistic effects have been observed when it is administered in combination with other antineoplastic agents. Clinically irinotecan is now an active agent in patients with colorectal carcinoma. Irinotecan is metabolized by carboxylesterase to an active metabolite. It is cleared by hepatic metabolism and biliary excretion with a terminal elimination half-life of approximately 15 hours. The principal toxicities associated with irinotecan are diarrhoea and leucopenia. 

Unlike isotretinoin, acitretin (Soriatane) is not primarily sebosuppressive. Rather, it promotes normalization of dysregulated keratinocyte proliferative activity in the epidermis and is also antiinflammatory. Oral absorption is optimal when acitretin is taken with a fatty meal peak levels are reached approximately 3 hours after ingestion, while steady-state plasma levels are achieved after approximately 3 weeks of daily dosing. The mean terminal elimination half-life of the parent compound is 49 hours. However, when consumed with ethanol, acitretin may be transesterifled to form etretinate, a retinoid that is stored in adipose tissue, resulting in a much longer half-life (3-4 months or longer). 

Chloroquine is a synthetic 4-aminoquinoline (Figure 52-2) formulated as the phosphate salt for oral use. It is rapidly and almost completely absorbed from the gastrointestinal tract, reaches maximum plasma concentrations in about 3 hours, and is rapidly distributed to the tissues. It has a very large apparent volume of distribution of 100-1000 /kg and is slowly released from tissues and metabolized. Chloroquine is principally excreted in the urine with an initial half-life of 3-5 days but a much longer terminal elimination half-life of 1-2 months. 

Pentamidine is an aromatic diamidine (Figure 52-3) formulated as an isethionate salt. Pentamidine is only administered parenterally. The drug leaves the circulation rapidly, with an initial half-life of about 6 hours, but it is bound avidly by tissues. Pentamidine thus accumulates and is eliminated very slowly, with a terminal elimination half-life of about 12 days. The drug can be detected in urine 6 or more weeks after treatment. Only trace amounts of pentamidine appear in the central nervous system, so it is not effective against central nervous system African trypanosomiasis. Pentamidine can also be inhaled as a nebulized powder for the prevention of pneumocystosis. Absorption into the systemic circulation after inhalation appears to be minimal. The mechanism of action of pentamidine is unknown. 

Suramin is a sulfated naphthylamine that was introduced in the 1920s. It is the first-line therapy for early hemolymphatic East African trypanosomiasis ( brucei rhodesiense infection), but because it does not enter the central nervous system, it is not effective against advanced disease. Suramin is less effective than pentamidine for early West African trypanosomiasis. The drug s mechanism of action is unknown. It is administered intravenously and displays complex pharmacokinetics with very tight protein binding. Suramin has a short initial half-life but a terminal elimination half-life of about 50 days. The drug is slowly cleared by renal excretion. 

After a single oral administration of 0.4 mg radiolabeled moxidectin/kg bw to horses, a mean peak serum concentration of 0.134 ppm moxidectin equivalents was attained at 6 h postdose (63). Oral availability was estimated at 40%, while the terminal elimination half-life was approximately 80 h. Within 168 h, 77% of the total radioactivity was excreted mostly by Ure fecal route. In feces, the parent drug represented approximately 70% of the fecal radioactivity, whereas a fraction of 0.28-3.45% was due to four minor metabolites resulting from oxidation mainly on Ci4, C24, and/or C28 positions. 

Pharmacokinetic properties Remifentanil is an ultra-short acting compound (Michelsen and Hug, 1996), rapidly inactivated by plasma and tissue esterases. The terminal elimination half-life is 10-20 min. 

Oral bioavailability is about 59% and is unaffected by meals. Peak serum levels occur at a median of 1.75 hours after dosing, and the terminal elimination half-life is approximately 7.5 hours. Protein binding is less than 4%. Adefovir is renally excreted by a combination of glomerular filtration and active tubular secretion. Dosing interval should be modified in patients with impaired renal... 

The drug s mechanism of action is unknown. It is administered intravenously and displays complex pharmacokinetics with very tight protein binding. It has a short initial half-life but a terminal elimination half-life of about 50 days. The drug is slowly cleared by renal excretion. 

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