Gastrointestinal drugs drug excretion

The majority of evidence supporting the pH-partition hypothesis is from studies of gastrointestinal absorption, renal excretion, and gastric secretion of drugs [11]. While correlation between absorption rate and pKa was found to be consistent with the pH-partition hypothesis, deviations from this hypothesis were often reported [12]. Such deviations were explained by the existence of a mucosal unstirred layer [13,14] and/or a microclimate pH [15]. 

Buspirone is well absorbed from the gastrointestinal tract, and peak blood levels are achieved in 1 to 1.5 hours the drug is more than 95% bound to plasma proteins. Buspirone is extensively metabolized, with less than 1% of the parent drug excreted into the urine unchanged. At least one of the metabolic products of buspirone is biologically active. The parent drug has an elimination half-life of 4 to 6 hours. 

The drug is given orally and is well absorbed from the gastrointestinal tract. It is rapidly metabohzed, and only low levels are found in blood and tissues. The drug is excreted in the urine, primarily in the form of metabolites. 

Figure 3.2 Schematic of distribution and elimination of pharmaceutical compound on normal administration. Compound is distributed through the (a) lungs, (b) arteries, (c) other tissues (e.g., muscles, subcutenous tissues), (d) veins, and (e) gastrointestinal tract (i.e., oral). Notice the enteroheptic cycle where recirculation occurs between the hver and the GIT with most of the drug being excreted in the bile and is released into the gall bladder, transits into the small intestine, and is absorbed into the circulatory system.

Drugs of the neomycin group are poorly absorbed from the gastrointestinal tract. After oral administration, the intestinal flora is suppressed or modified, and the drug is excreted in the feces. Excretion of any absorbed drug is mainly through glomerular filtration into the urine. 

In species where reabsorption of drugs from the gastrointestinal tract increases the half-life of elimination, salivary secretion represents another important excretion route. The large volume of alkaline saliva produced by ruminants offers the possibility of trapping the acidic drugs. Exhalation of products of drug metabolism, such as carbon dioxide and water, can also account for drug excretion. 

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

Pharmacokinetics Bretylium is poorly absorbed from the gastrointestinal tract and therefore is usually administered parenter-ally. The drug is excreted unchanged in the urine, and dosage may have to be adjusted in patients with kidney dysfunctions. 

Because it is not absorbed on oral administration, sodium stibogluconate must be administered parenterally. It is distributed in the extravascular compartment. Metabolism is minimal and the drug is excreted into the urine. Adverse effects include pain at the injection site, gastrointestinal upsets, and cardiac arrhythmias. Renal and hepatic function should be periodically monitored. 

Docusate salts are absorbed from the gastrointestinal tract and excreted in bile they may cause alteration of the gastrointestinal epithelium. The gastrointestinal or hepatic absorption of other drugs may also be affected by docusate salts, enhancing activity and possibly toxicity. Docusate sodium should not be administered with mineral oil as it may increase the absorption of the oil. 

In humans, the half-life of aerosolized albuterol sulfate is approximately 4 h. The kidney is the primary site of elimination with the majority of the drug excreted as sulfide and glucuronide metabolites (61%) and the remainder (39%) excreted unchanged. The absorption of albuterol from the gastrointestinal tract is poor (20% bioavailability) the primary site of absorption into the systemic circulation is the pulmonary system. There are currently no data available on the pharmacokinetics of albuterol in horses. 

Ciassification and pharmacokinetics Amphotericin B is a polyene antibiotic related to nystatin. Amphotericin is poorly absorbed from the gastrointestinal tract and is usually administered intravenously as a colloidal suspension, or in some cases in a lipid formulation. The drug is widely distributed to all tissues except the CNS. Elimination is mainly via slow hepatic metabolism the half-life is approximately 2 weeks. A small fraction of the drug is excreted in the urine, dosage modification is necessary only in extreme renal dysfunction. Amphotericin B is not dialyzable. 

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