Drug administration serum concentrations

Oral absorption of carbamazepine is quite slow and often erratic. Its half-life is reported to vary from 12 to 60 hours in humans. The development of blood level assays has markedly improved the success of therapy with this drug, since serum concentration is only partially dose related. Carbamazepine is metabolized in the liver, and there is evidence that its continued administration leads to hepatic enzyme induction. Carbamazepine-10,11-epoxide is a pharmacologically active metabolite with significant anticonvulsant effects of its own. 

Although the terminal half-life of cidofovir is about 2.6 hours, the active metabolite, cidofovir diphosphate, has a prolonged intracellular half-life of 17-65 hours, thus allowing widely spaced administration. A separate metabolite, cidofovir phosphocholine, has a half-life of at least 87 hours and may serve as an intracellular reservoir of active drug. Peak serum concentrations when administered with probenecid (see Clinical Uses) are about 19 g/mL. Cerebrospinal fluid penetration is poor after intravenous administration. Elimination involves active renal tubular secretion. High-flux hemodialysis has been shown to reduce the serum levels of cidofovir by approximately 75%. 

Additive bone marrow depressive effects occur when the miotic inhibitor drugs are administered with other anti-neoplastic dragp or radiation therapy. Administration of vincristine with digoxin results in a decreased therapeutic effect of tlie digoxin and decreased plasma digoxin levels. There is a decrease in serum concentrations of phenytoin when administered widi vinblastine... 

Flutamide is an androgen receptor antagonist that achieves peak concentrations approximately 2 to 4 hours after an oral dose. Flutamide is metabolized extensively, with a terminal half-life of about 8 hours. Bicalutamide achieves peak concentrations approximately 6 hours after the dose, with a terminal half-life of 6 to 10 days. Bicalutamide undergoes stereospecihc metabolism, where the S-enantiomer is cleared more rapidly by the liver than the -enantiomer. Nilutamide achieves peak serum concentrations between 1 to 4 hours after an oral dose and has a terminal half-life of 38 to 60 hours. Nilutamide is metabolized extensively, with less than 2% excreted as unchanged drug by the kidney. Side effects common to these agents are hot flashes, gynecomastia, and decreased libido. Flutamide tends to be associated with more diarrhea and requires three-times-daily administration, whereas bicalutamide is dosed once daily. Nilutamide may cause interstitial pneumonia and is associated with the visual disturbance of delayed adaptation to darkness. 

Factors directly related to the drug selection include an inappropriate selection of drug, dosage, or route of administration. Malabsorption of a drug product because of GI disease (e.g., short-bowel syndrome) or a drug interaction (e.g., complexation of fluoroquinolones with multivalent cations resulting in reduced absorption) may lead to potentially subtherapeu-tic serum concentrations. 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

To allow adequate time for equilibration of digoxin between serum and tissue, perform sampling of serum concentrations just before the next scheduled dose of the drug. If this is not possible, perform sampling at least 6 to 8 hours after the last dose, regardless of the route of administration or the formulation used. 

Begin drug administration as soon as possible after suspected or confirmed exposure to B. anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit. Total duration c ciprofloxacin administration (IV, IR, or oral) for inhalational anthrax (postexposure) is 60 days. 

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone. 

Most of the drug interactions with carbamazepine are related to its effects on microsomal drug metabolism. Carbamazepine can induce its own metabolism (autoinduction) after prolonged administration, decreasing its clearance rate, half-life, and serum concentrations. The possibility of autoinduction requires the clinician to reevaluate the patient s blood levels after a month of carbamazepine therapy. The autoinduction phenomenon is over in about a month. 

Orally administered ethambutol is well absorbed (70-80%) from the gut, and peak serum concentrations are obtained within 2 to 4 hours of drug administration it has a half-life of 3 to 4 hours. Ethambutol is widely distributed in all body fluids, including the cerebrospinal fluid, even in the absence of inflammation. A majority of the unchanged drug is excreted in the urine within 24 hours of ingestion. Up to 15% is excreted in the urine as an aldehyde and a dicarboxylic acid metabolite. Ethambutol doses may have to be modified in patients with renal failure. 

Praziquantel is readily absorbed (80% in 24 hours) after oral administration, with serum concentrations being maximal in 1 to 3 hours the drug has a half-life of 0.8 to 1.5 hours. Its bioavailability is reduced by pheny-toin or carbamazepine and increased by cimetidine. Dexamethasone decreases plasma praziquantel levels by 50%. Praziquantel is excreted by the kidneys. 

Aminoglycosides are absorbed very poorly from the intact gastrointestinal tract almost the entire oral dose is excreted in feces after oral administration. However, the drugs may be absorbed if ulcerations are present. After intramuscular injection, aminoglycosides are well absorbed, giving peak concentrations in blood within 30-90 minutes. Aminoglycosides are usually administered intravenously as a 30- to 60-minute infusion after a brief distribution phase, this results in serum concentrations that are identical with those following intramuscular injection. 

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8-1.5 hours. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids. 

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. 

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