Oral administration renal clearance after

The p2-agonists are eliminated by metaboKsm and renal excretion. However, the relative importance of these pathways is highly dependent on the route of administration. Following parenteral administration, renal clearance is the predominant pathway of elimination. In contrast, metabolism becomes more important after their oral administration. Drastically lower intact drug concentrations in plasma and urine after the oral administration of these antiasthma agents reflect an extensive first-pass metabolism in the gastrointestinal tract [121]. 

After either oral or intravenous administration of ondansetron to laboratory animals the elimination of the drug is rapid. The short elimination half-lives t ji Table 7.7) reflect the high plasma clearance (CLp) in these species. Renal clearance (CLr) is below glomerular filtration rate, indicating that the major component of systemic clearance is metabolism. Ondansetron is rapidly absorbed after oral administration, peak concentrations in plasma being achieved within 40 min of dosing. However, the oral bioavailability is low. The similarity between concentrations of total drug-related material in plasma after oral and intravenous doses indicates that the low... 

Excretion - The plasma half-life for trospium following oral administration is approximately 20 hours. After administration of oral trospium, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8%) was recovered in urine 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29.07 L/h) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that also are renally eliminated. 

Elderly Mean penciclovir AUC was 40% larger and penciclovir renal clearance was 22% lower after the oral administration of famciclovir in elderly volunteers compared with younger volunteers. 

Excretion - Absorbed oseltamivir is primarily (more than 90%) eliminated by conversion to oseltamivir carboxylate. Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration. Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects. Oseltamivir carboxylate is eliminated entirely (more than 99%) by renal excretion. Renal clearance (18.8 L/h) exceeds glomerular filtration rate (7.5 L/h) indicating that tubular secretion occurs, in addition to glomerular filtration. Less than 20% of an oral dose is eliminated in feces. 

J. Ekstrand, M. Ehrnebo, L.O. Boreus, Fluoride bioavailability after intravenous and oral administration Importance of renal clearance and urine flow/, Clin. Pharmacol. Ther. 23 (1978) 329-337. 

All thiazides and related compounds are well absorbed from the GIT and begin to produce diuresis within one hour after oral administration, but the duration is variable, which are due to variation in rates of renal tubular secretion and clearance, metabolism, and enterohepatic circulation. Approximately 50 percent of an oral dose is excreted in urine within 6 hours. Most of the agents undergo little hepatic metabolism and excreted as such. However indapamide is extensively metabolized. 

Maximal plasma concentrations occur 2 to 3 hours after oral administration of reboxetine (178). Reboxetine has linear pharmacokinetics over its clinically relevant dosing range and a half-life of approximately 12 hours. For this latter reason, a twice a day, equally divided dosing schedule was used during clinical trial development. Its clearance is reduced and half-life becomes longer as a function of advanced age (mean = 81 years of age) and renal and hepatic impairment ( 178, 322, 323). Reboxetine is principally metabolized by CYP 3A3/4 such that its dose should be reduced when used in combination with drugs that are substantial inhibitors of CYP (e.g., certain azole antifungals, certain macrolide antibiotics). Reboxetine itself, however, does not cause detectable inhibition of CYP 3A3/4 based on formal in vivo pharmacokinetic interaction studies as well as its own linear pharmacokinetics. 

Figure 7 Change in the biliary and renal clearance of digoxin caused by quinidine or quinine treatment. After a steady state concentration of quinine or quinidine was achieved by multiple oral administrations, the plasma concentration and biliary and urinary excretion of digoxin after oral administration were measured in healthy volunteers. The steady state concentrations of quinine and quinidine were 7.0 2.5 and 4.5 0.5 pM, respectively. Source From Ref. 291.

Fig. 17.4 Impact of sex and creatinine clearance on the plasma concentration-time profiles of NS2330 after oral administration of lmg NS2330 once daily for 166 days (4000 h). Typical profiles of a male subject with normal renal function, a female subject with normal and reduced renal function.

Pharmacokinetics Sildenafil is rapidly absorbed after oral administration, and peak plasma levels are achieved within one hour. Bioavailability is about 40 percent of the oral dose. Sildenafil enters tissues, and has an apparent volume of distribution of 1.5 L/kg. Both sildenafil and its major N-desmethylated metabolite are > 95 percent bound to plasma proteins. Both CYP3A4 (major route) and CYP2C9 (minor route) are responsible for the metabolism of sildenafil. The major metabolite, N-desmethyl sildenafil, is approximately 50 percent as potent as sildenafil in inhibiting PDE5. The major route of elimination for sildenafil and its metabolites is via the bile. Clearance is decreased in older individuals free plasma concentrations are 40 percent higher in healthy volunteers > 65 years old. Severe renal impairment (< 30 mL/min) increases the AUC (see p. 7) by two-fold. Similarly, cirrhosis of the liver also significantly increases the AUC. 

Disposition in the Body. Readily absorbed after oral administration. Acetazolamide binds tightly to carbonic anhydrase and will accumulate in tissues in which this enzyme is present, particularly in red blood cells and the renal cortex. About 70 to 90% of a dose is excreted in the urine as unchanged drug in 24 hours but the renal clearance is increased if the urine is alkaline small amounts of unchanged drug are excreted in the bile. 

After oral administration sitafloxacin 500 mg is rapidly absorbed, with a systemic availability of 89% (3). By 48 hours, about 61% is excreted unchanged in the urine after oral administration and about 75% after intravenous administration. For both routes, the high renal clearance of sitafloxacin implies active tubular secretion. 

Absorption of procainamide is rapid and complete. Peak plasma concentrations after oral administration are reached within 0.75 to 1.5 hours if the drug is given in capsule form or within 1 to 3 hours if given in tablet form. Once absorbed, procainamide is about 20% bound to plasma proteins. Excretion of procainamide depends on hepatic metabolism by Al-acetyltransferase (NATl) and renal clearance therefore alteration in either organ function leads to accumula-... 

Absorption of quinidine is complete and rapid. Peak serum concentrations are reached in 1.5 to 2 hours after oral intake, unless the slow-release preparation (quinidine gluconate) is used. Peak plasma concentrations are attained 4 to 5 hours after quinidine gluconate administration, and the trough concentration occurs 1 to 2 hours after the next administration. Once absorbed, quinidine is 80% protein bound. Metabolism of quinidine is by CyP 3A4. Clearance of quinidine depends on adequate hepatic and renal function. Reduction of either of these two functions results in accumulation of the drug. Renal clearance is a function of urine pH. If the urine is alkaline or if a patient has renal tubular acidosis, clearance is reduced. 

Candesartan cilexetil (Atacand) This cilexetil is an inactive ester prodrug that is completely hydrolyzed to the active form, candesartan, during absorption from the gastrointestinal tract. Peak plasma levels are obtained 3 to 4 hours after oral administration, and plasma half-hfe is about 9 hours. Plasma clearance of candesartan is due to renal elimination (33%) and biliary excretion (67%). Candesartan cilexetil should by administered orally once or twice daily for a total daily dosage of 4 to 32 mg. 

Eprosartan (Teveten) Peak plasma levels are obtained approximately 1 to 2 hours after oral administration, and the plasma half-life ranges from 5 to 9 hours. Eprosartan is metabolized in part to the glucuronide conjugate, and the parent compound and its glucuronide conjugate are cleared by renal elimination and biliary excretion. The plasma clearance of eprosartan is affected by both renal insufficiency... 

Oral administration of etoposide results in variable absorption that averages about 50%. After intravenous injection, peak plasma concentrations of 30 pg/mL are achieved there is a biphasic pattern of clearance with a terminal half-hfe of about 6 to 8 hours in patients with normal renal function. Approximately 40% of an administered dose is excreted intact in the urine, hi patients with compromised renal function, dosage should be reduced in proportion to the reduction in... 

Following oral administration, lamivudine is absorbed rapidly with a bioavailability of about 80% in adults. Peak plasma levels average approximately 1000 ng/mL after 100-mg doses. Lamivudine is distributed widely in a volume comparable with total-body water. The plasma t,/2 of elimination averages about 9 hours, and approximately 70% of the dose is excreted unchanged in the urine. About 1% is metabolized to an inactive trawY-sulfoxide metabolite. In HBV-infected children, doses of 3 mg/kg per day provide plasma exposure and trough plasma levels comparable with those in adults receiving 100 mg daily. Dose reductions are indicated for moderate renal insufficiency (creatinine clearance <50 ml/min). Trimethoprim decreases the renal clearance of lamivudine. 

Telmisartan (Micardis) Peak plasma levels are obtained approximately 0.5 to 1 hour after oral administration and the plasma half-life is about 24 hours. Telmisartan is cleared from the circulation mainly by biliary secretion of intact drug. The plasma clearance of telmisartan is affected by hepatic but not renal insufficiency. The recommended oral dosage of telmisartan is 40 to 80 mg once daily. 

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