Drug metabolism, pharmacokinetic renal disease

Pharmacokinetics Slow intravenous infusion is employed for treatment of systemic infections or for prophylaxis. Because vancomycin is not absorbed after oral administration, this route is only employed for the treatment of antibiotic-induced colitis due to Q difficile. Inflammation allows penetration into the meninges. Metabolism is minimal 90-100 % is excreted by glomerular filtration. [Note Dosage must be adjusted in renal failure since the drug will accumulate. Normal half-life is 6-10 hours compared to over 200 hours in end-stage renal disease.]... 

Diseases such as hepatic or renal diseases can influence the incidence of ADRs by altering the pharmacokinetics of drugs, such as absorption, distribution, metabolism, or excretion. 

The absolute bioavailability of only a few drug compounds is affected by ESKD. An increase in bioavailability as the result of a decrease in metabolism during the drug s firstpass through the gastrointestinal tract and liver has been noted for some /3-blockers (i.e., bufu-ralol, oxprenolol, propranolol, and tolamolol), dextropropoxyphene, and dihydrocodeine. Although the bioavailability of these compounds is increased, clinical consequences (development of excessive or unexpected adverse effects) have only been demonstrated with dextropropoxyphene and dihydrocodeine. The lack of association between the pharmacokinetic profile and clinical consequences of the /3-blockers may result from an alteration in the responsiveness of patients with renal disease to these agents, as has been reported with propranolol in the elderly. ... 

For drugs that are primarily cleared by liver, there is a misconception that hepatic drug disposition will be unaffected by renal disease. Accumulating evidence has shown that deterioration of kidney function significantly reduces nonrenal clearance and alters the pharmacokinetics of some drugs that are predominantly metabolized or eliminated by liver through modulation... 

Angiotensin-converting enzyme (ACE) inhibitors, angiotensin-11 receptor blockers (ARBs), P-blockers, and calcium channel blockers are not dosed in the clinical setting using pharmacokinetic equations. The clinical use and selection of a drug within a class of medications is determined, in part, on differences in pharmacokinetic parameters. Eor example, metoprolol is commonly used in patients with renal disease because it is metabolized in the liver. Atenolol is avoided because it is renally eliminated. Select pharmacokinetic parameters for ACE inhibitors, ARBs, P-blockers, and calcium channel blockers are listed in Tables 8.11 through 8.13. 

Clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram are extensively metabolized in the Liver, and patients with significant liver disease should be prescribed these drugs cautiously and in lower doses than those used in healthy subjects. The pharmacokinetics of fluoxetine and fluvoxamine were similar in patients with renal faUme and in healthy subjects however, the manufacturer recommends starting with a lower dose in patients with renal impairment. The pharmacokinetics of sertraline are not altered in patients with significant renal dysfunction, and dosage adjustment is not necessary in these patients. Increased plasma concentrations of paroxetine occur in subjects with renal impairment. The initial dose of paroxetine should be reduced in patients with severe renal impairment, and upward titration should occm more slowly. No dosage adjustment is necessary for patients with mild to moderate renal impairment receiving citalopram. 

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