Distribution, drug parenteral administration

These results indicate that, in addition to effectiveness by inhalation and parenteral administration, SNA is well absorbed in man when administered orally. The drug is 60-70% bound to plasma proteins, the volume of distribution is high (approximately 500 L In an 80-kg man), clearance is largely a result of metabolic processes, the half-life Is quite variable from one person to another, and the drug and its metabolites are excreted principally in the urine, regardless of whether it is given orally or intravenously. 

Phenothiazines are well absorbed after oral and parenteral administration. They are distributed in all the body tissues and metabolised in liver by hydroxylation and glucuronide conjugation and demethylation. The metabolites are excreted in urine and bile for long period of time even after discontinuing the drug. 

Disposition in the Body. Rapidly distributed in the tissues following parenteral administration. About 90% of a dose is excreted in the urine in 72 hours, with about 2% of the dose as unchanged drug, 2% as norketamine, 16% as dehydronorke-tamine, and 80% as conjugates of hydroxylated metabolites. Norketamine (which has about one-sixth of the potency of ketamine) and dehydronorketamine are found in the serum in concentrations similar to those of ketamine. It has been suggested that dehydronorketamine may be an analytical artefact rather than a metabolite. 

Significant differences in the extent of distribution of drugs, particularly lipid-soluble organic bases, are usual between ruminant and monogastric species. After parenteral administration, lipophilic bases diffuse passively from the systemic circulation into ruminal fluid (pH 5.5-6.5), where they become trapped by ionization. These drugs are slowly reabsorbed or, if they possess fimctional groups suitable for metabolism by hydrolysis or reduction, they may be partially inactivated by ruminal micro-organisms. 

Drug Metabolic Products - Pharmacokinetics Cephalothin was partially converted to deacetylcephalothin after parenteral administration to experimental animals and to man.23 in the dog, initial excretion was distributed equally between cephalothin and its deacetyl metabolite later excretion showed a preponderance of the metabolite over the parent compound. Cephalothin persisted over a longer period of time when administered by the intramuscular route than when given intravenously. In man, the total amount excreted in the urine was... 

ABSORPTION, DISTRIBUTION, AND EXCRETION Isoniazid is readily absorbed after oral or parenteral administration. Isoniazid diffuses readily into aU body fluids and cells. The drug achieves significant quantities in pleural and ascitic fluids concentrations in the cerebrospinal fluid (CSF) with inflamed meninges are similar to those in the plasma. Isoniazid penetrates well into caseous material and persists in therapeutic concentrations. 

The most widely used parenteral administration avenues are intravenous (iv), intramuscular (im), and subcutaneous (sc). In addition, there are several minor applications (e.g. intraarterial). Application of a protein drug by the different main parenteral administration routes may have profound effects on the pharmacological performances. When the drug is administered iv, it is immediately available for action in the circulation, while drugs administered im or sc need more time to reach the blood (depot effect), and consequently the pharmacokinetic (PK) profiles could be different. Besides the PK, the route of administration may have influence on the primary distribution of the drug. For example, when administered sc, smaller and hydrophiUic proteins tend to enter the venous system, while larger and/or more hydrophobic proteins tend to... 

The pharmacokinetic properties of aztreonam are similar to those of the parenteral cephalosporins (Table 45.2). Aztreonam is not bioavailable after oral administration. During its distribution phase, the drug can achieve therapeutic concentrations in cerebrospinal fluid in the presence of inflamed meninges. Consequently, aztreonam is an alternative antibiotic to the cephalosporins for the therapy of meningitis caused by gram-negative bacilli. 

The usual dosage of chloramphenicol is 50-100 mg/kg/d. After oral administration, crystalline chloramphenicol is rapidly and completely absorbed. A 1-g oral dose produces blood levels between 10 and 15 mcg/mL. Chloramphenicol palmitate is a prodrug that is hydrolyzed in the intestine to yield free chloramphenicol. The parenteral formulation is a prodrug, chloramphenicol succinate, which hydrolyzes to yield free chloramphenicol, giving blood levels somewhat lower than those achieved with orally administered drug. Chloramphenicol is widely distributed to virtually all tissues and body fluids, including the central nervous system and cerebrospinal fluid, such that the concentration of chloramphenicol in brain tissue may be equal to that in serum. The drug penetrates cell membranes readily. 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

There are certain limitations with cosolvent approach, as with any other approaches, as poor tasting cosolvent (PG), adverse physiological effects (e.g., alcohol) and potential of cosolvent on metabolic enzymes, transporters, and distribution and hence unintentionally altering drug pharmacokinetic properties. For solubilized parenteral application, choice of cosolvents is further limited by physiological acceptance, as well as precipitation on injection and pain on administration. However, the approach remains popular both for oral as well as parenteral application as demonstrated by numerous commercial products. In addition, application of newer cosolvents is increasing to overcome some of these barriers. 

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. 

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