Pharmacokinetics renal elimination

Renal elimination of unchanged drug accounts for 66% of drug clearance, and the dose should be adjusted for impaired renal function. The role of therapeutic drag monitoring is unknown. It has linear pharmacokinetics and is metabolized in blood by nonhepatic enzymatic hydrolysis. 

Pharmacokinetics Venlafaxine is well absorbed (at least 92%) and extensively metabolized in the liver. ODV is the only major active metabolite. Renal elimination of venlafaxine and its metabolites is the primary route of excretion. Venlafaxine ER provides a slower rate of absorption but the same extent of absorption compared with the immediate-release tablet. 

Some penicillins cannot be given orally as their beta-lactam ring is hydrolyzed and inactivated in the stomach by gastric acid. In general intramuscular injections are painful and therefore not advised. The pharmacokinetic behavior of penicillins is further characterized by short elimination half-lives. Renal elimination is prominent. 

Penicillin G is excreted by the kidneys, with 90% of renal elimination occurring via tubular secretion and 10% by glomerular filtration. Probenecid blocks tubular secretion and has been used to increase the serum concentration and prolong the half-life of penicillin G and other penicillins. Additional pharmacokinetic information can be found in Table 45.1. 

Pharmacokinetics Oral. Maximum serum concentrations attained within 3 hours. Protein binding-. 96%-99%. Metabolized in liver. Excreted in bile and urine. Half-life 18.3 hr. IM Rapidly absorbed. Undergoes rapid metabolism. Half-life Few min. Long-acting form Approximately 10 wk. Vaginal Gel Rate limited by absorption rather than by elimination. Protein binding-. 96%-99%. Undergoes both biliary and renal elimination. Half-life 5-20 hr. 

The mean elimination half-life is about 6 h. The O-demethylation of tramadol to Ml, the main analgesic effective metabolite, is catalyzed by cytochrome P450 (CYP) 2D6, whereas A-demeth-ylation to M2 is catalyzed by CYP2B6 and CYP3A4. The wide variability in the pharmacokinetic properties of tramadol can partly be ascribed to CYP polymorphism. O- and A-demethylation of tramadol as well as renal elimination are stereoselective.56... 

Extracellular MRI and X-ray contrast agents are characterized by their pharmacokinetic behaviour. After intravascular injection their plasma-level time curve is characeterized by two phases. The agents are rapidly distributed between plasma and interstitial spaces followed by renal elimination with a terminal half-live of approximatly 1-2 hours. They are excreted via the kidneys in unchanged form by glomerular filtration. 

Tett SE, Kirkpatrick CM, Gross AS, McLachlan AJ. Principles and clinical application of assessing alterations in renal elimination pathways. Clin Pharmacokinet. 2003 42 1193-1211. 

Animal studies indicating that the drug candidate is primarily eliminated renally and/or physicochemical characteristics making a renal elimination likely are flags suggesting the need to profile candidate drug pharmacokinetics in elderly - since some degree of renal impairment is often observed in this population. 

Primaquine is rapidly absorbed, extensively distributed, and predominantly cleared by non-renal elimination. Its principal metabolite is carboxyprimaquine. While primaquine itself is rapidly eliminated from the plasma, the drug is effective when given once daily or even once weekly (SEDA-13, 810). The pharmacokinetics in children, pregnant women, and patients with renal or hepatic dysfunction are unknown. 

Pathogenic mechanism of auranofin-induced nephropathy resemble those of parenteral gold-induced nephropathy. The reason for the reduced risk of proteinuria with auranofin compared to parenteral gold salts is not known. However, differences in the pharmacokinetics of the two types of gold preparations may be important. In rats treated with auranofin or sodium aurothiomalate for one year, renal gold concentrations were 33 times higher with the latter formulation [85]. Renal elimination of an orally administered dose of auranofin in human is less than 15%, compared with greater than 70% for parenterally administered sodium aurothiomalate [86]. 

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