Intravenous administration bioavailability

Bioavailability is the amount of drug in a formulation that is released and becomes available for absorption or the amount of the drug absorbed after oral administration compared to the amount absorbed after intravenous administration (bioavailability - 100%), judged from areas remaining under plasma drug concentration-time curves. 

To express the extent to which and at what rate a drug reaches the systemic circulation, the term bioavailability is used. Bioavailability of a drug is (1) the fraction of the administered dose which reaches the systemic circulation and (2) the rate at which this occurs. After intravenous administration bioavailability is by definition 100% for all other routes of administration, the bioavailability can vary between 0 and 100%. 

Area under the Curve (AUC) refers to the area under the curve in a plasma concentration-time curve. It is directly proportional to the amount of drug which has appeared in the blood ( central compartment ), irrespective of the route of administration and the rate at which the drug enters. The bioavailability of an orally administered drug can be determined by comparing the AUCs following oral and intravenous administration. 

In the total plasma response approach, the bioavailability of a compound is determined by measuring its plasma concentration at different times (up to weeks) after single or long-term ingestion of the compound from supplements or food sources. Generally, a plasma concentration-versus-time plot is generated, from which is determined the area-under-curve (AUC) value used as an indicator of the absorption of the componnd. Here, the term relative bioavailability is more appropriate since AUC valnes of two or more treatments are usually compared. This is in contrast to absolnte bioavailability for which the AUC value of the orally administered componnd is compared to that obtained with intravenous administration taken as a reference (100% absorption). 

The AUC is a measure of bioavailability, i.e. the amount of substance in the central compartment that is available to the organism. It takes a maximal value under intravenous administration, and is usually less after oral administration or parenteral injection (such as under the skin or in muscle). In the latter cases, losses occur in the gut and at the injection sites. The definition also shows that for a constant dose D, the area under the curve varies inversely with the rate of elimination kp and with the volume of distribution V. Figure 39.6 illustrates schematically the different cases that can be obtained by varying the volume of distribution Vp and the rate of elimination k both on linear and semilogarithmic diagrams. These diagrams show that the slope (time course) of the curves are governed by the rate of elimination and that elevation (amplitude) of the curve is determined by the volume of distribution. 

Intravenous antibiotic administration is the most common delivery method for surgical prophylaxis. Intravenous administration ensures complete bioavailability while minimizing the impact of patient-specific variables. Oral administration is also used in some bowel operations. Non-absorbable compounds like erythromycin base and neomycin are given up to 24 hours prior to surgery to cleanse the bowel. Note that oral agents are used adjunctively and do not replace IV agents. 

Etoposide causes multiple DNA double-strand breaks by inhibiting topoisomerase II. The pharmacokinetics of etoposide are described by a two-compartment model, with an a half-life of 0.5 to 1 hour and a (5 half-life of 3.4 to 8.3 hours. Approximately 30% of the dose is excreted unchanged by the kidney.16 Etoposide has shown activity in the treatment of several types of lymphoma, testicular and lung cancer, retinoblastoma, and carcinoma of unknown primary. The intravenous preparation has limited stability, so final concentrations should be 0.4 mg/mL. Intravenous administration needs to be slow to prevent hypotension. Oral bioavailability is approximately 50%, so oral dosages are approximate two times those of intravenous doses however, relatively low oral daily dosages are used for 1 to 2 weeks. Side effects include mucositis, myelosuppression, alopecia, phlebitis, hypersensitivity reactions, and secondary leukemias. 

N. A., Flink, O., Paalzow, L., Ampicillin comparison of bioavailability and pharmacokinetics after oral and intravenous administration of three brands, Eur. J. Clin. Pharmacol. 1976, 30, 237-243. 

The bioavailability of a dosage form relative to an intravenous administration. 

Intravenous Administration When a drug is injected, the entire dose can be considered as being available in the bloodstream to be distributed to the target site. Hence, the dosage can be controlled, unlike with other routes of administration, where the bioavailability of the drug may be unpredictable because of diffusion processes. Intravenous injection is the normal route for administration of protein-based drugs, as they are likely to be destroyed if taken orally because of the pH conditions in the gastrointestinal tract. 

After either oral or intravenous administration of ondansetron to laboratory animals the elimination of the drug is rapid. The short elimination half-lives t ji Table 7.7) reflect the high plasma clearance (CLp) in these species. Renal clearance (CLr) is below glomerular filtration rate, indicating that the major component of systemic clearance is metabolism. Ondansetron is rapidly absorbed after oral administration, peak concentrations in plasma being achieved within 40 min of dosing. However, the oral bioavailability is low. The similarity between concentrations of total drug-related material in plasma after oral and intravenous doses indicates that the low... 

It can be assumed that the bioavailability of an intravenous dose is 100% and a calculation of oral bioavailability can therefore be obtained by comparison of the AUCs after oral and intravenous administration, after correction for the exact dose ... 

Much remains to be done to improve the physicochemical properties and the pharmacokinetic characteristics of the estabhshed compound classes. A critical observer cannot help but wonder about the PK/PD profiles of many of the compoimds currently undergoing chnical development with hmited oral bioavailability, often necessitating intravenous administration, and rather short half fives in combination with often transient acetylation effects, the need for HDAC inhibitors with a more beneficial pharmacokinetic profile seems key. 

Clindamycin can be administered orally with a high bioavailability. Also formulations for intravenous administration exist. Protein binding is about 90%. It is distributed throughout the body except the CNS. It shows excellent penetration in bone and in empyema and abscesses. It is metabolized in the liver and excreted in the bile. The elimination half-life is about 3 h. Adverse effects include gastrointestinal distress, skin rashes and decreased liver function. Pseudomembranous colitis is relatively frequently seen due to resistance of Clostridium difficile. 

These antibiotics are considered as a choice of last resort where every other antibiotic therapy has failed. The first and only commercially available oxazolidinone antibiotic is linezolid which was introduced in 2002. Its mechanism of action is inhibition of bacterial protein synthesis. It is available for intravenous administration and also has the advantage of having excellent oral bioavailability. Linezolid is used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRS A). 

Imipenem-cilastatin is only available for intramuscular or intravenous administration because oral bioavailability is poor. The enzyme, dehydropeptidase 1, present in renal tubules, converts imipenem to an inactive metabolite. To decrease metabolic clearance, imipenem is combined with cilastatin, an inhibitor of dehydropeptidase I. Additional pharmacokinetic information appears in Table 45.2. 

Any decrease in the total area under the curve for intramuscular or oral versus intravenous administration would represent a decrease in bioavailability based on that route of administration (16). Common factors that influence bioavailability include ... 

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