Parenteral administration bioavailability

Disposition in the Body. Rapidly absorbed after oral or parenteral administration bioavailability about 65%. Peak serum concentrations are achieved in about 2 hours. The main metabolic reactions are N- and O-demethylation and conjugation with glucuronic acid and sulphate. The major metabolites formed are... 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

H. Bundgaard, C. Larsen, E. Arnold, Prodrugs as Drug Delivery Systems XXVII. Chemical Stability and Bioavailability of a Water-Soluble Prodrug of Metronidazole for Parenteral Administration , Int. J. Pharm. 1984, 18, 79-87. 

The effectiveness of dihydroergotamine (DHE) and ergotamine tartrate was demonstrated in old clinical trials which probably would not meet currently accepted criteria for good methodology. For ergotamine tartrate, the dose usually recommended is 1-2 mg/d not to exceed 6 mg/d or 10 mg/week. DHE, which has a low bioavailability, is only effective after parenteral administration (subcutaneous, intramuscular, intravenous, or nasal-spray administration). The recommended dose is 1-2 mg/d. 

Enfuvirtide requires parenteral administration, and the peak levels are reached in about 4 h. Its bioavailability is 84%, and the drug is 92% protein-bound in plasma. Its half-life is 3.8 h, and enfuvirtide is metabolized in liver, which is not at significant levels. Enfuvirtide is approved for the treatment of HIV in patients whose response to antiretroviral therapeutic regimen is not satisfactory, and there is indication that HIV is still replicating. 

Bundgaard, H., C. Larsen, and E. Arnold. 1984a. Prodrugs as drug delivery systems. XXVII. Chemical stability and bioavailability of a water-soluble prodrug of metronidazole for parenteral administrated. 

Routine parenteral administration by injection serves to deliver drugs to specific body tissues. The most important routes of injection of these sterile products are intramuscular (im), intravenous (iv) and subcutaneous (sc). Basic parenteral formulation involves the selection of appropriate bases (e.g. aqueous, oily and emulsions) to achieve the desired bioavailability following injection. The detailed description of... 

The low oral bioavailability of hormone-replacement drugs due to intestinal and first-pass metabolism requires the use of higher doses of these drugs, which are associated with many side effects. Parenteral administration of sex steroids as well as use of the transdermal route has been viewed as an alternative. However, the transdermal route has certain limitations, such as the visibility and palpability of the patch as well as possible skin irritation. These drawbacks have limited the use of this route. The intranasal route has therefore been considered as an alternative [128],... 

Lecithin-based o/w MEs for parenteral use were formulated using polysorbate 80, IPM (Isopropyl myristate), lecithin, and water at different lecithin-polysorbate 80 weight ratios [115]. The formulated systems were shown to be highly stable and of minimal toxicity when evaluated in vitro. Phospholipid-based ME formulations of all-trans retinoic acid (ATRA) for parenteral administration were prepared and tested in vitro [116]. ATRA is effective against acute promyelocytic leukemia with highly variable oral bioavailability. Parenteral ME of ATRA was prepared using pharmaceutically acceptable ingredients, namely phospholipids and soybean oil. The inhibitory effect of ATRA on two human cancer cell lines (HL-60 and MCF-7) was not affected by incorporation into a ME formulation. 

Morphine Pain control as alternative to parenteral administration Tablet and vaginal suppository Requires close monitoring due to unpredictable bioavailability 337... 

In common with other phenolic opiate analgesics, buprenorphine shows low peroral potency, suggesting a high first-pass metabolism effect indeed, work in rats has shown this to be the case. Intravenous studies have estimated that the extraction ratio of buprenorphine is 85% and that peroral systemic availability is consequently expected to be 15% or less. Although absorption from the mouth is slow and, therefore, not as useful as parenteral administration in the treatment of acute pain, it offers a major bioavailability advantage over the peroral route for this drug. If required, the patient can be given a parenteral dose of buprenorphine to achieve rapid pain relief and... 

Although not routinely given by the buccal or sublingual routes, several research studies have shown that absorption of morphine from the mouth gives rise to effective analgesia and that these routes may provide suitable alternatives to parenteral administration. " Clinical studies have suggested that the bioavailability of morphine is 40-50% greater after buccal than intramuscular administration as plasma morphine... 

For over 70 years, approved insulin products have been given to diabetic patients exclusively by parenteral administration. Due to the challenges and obstacles associated with oral administration of peptide dmgs, no oral dosage form for insulin has been marketed to date.67 In general, studies of insulin s oral bioavailability have shown uptakes that range from near zero to a small percentage of the administered dose.68-75... 

Some of the key factors in considering specific delivery systems are safety, stability, and efficacy. The parenteral administration of proteins and peptides today offers assured levels of bioavailability and the ability of the product to reach the marketplace first. It is safe to assume that over 95% of the protein therapeutics approved by the Food and Drug Administration (FDA) today are injectable products since parenteral administration avoids physical and enzymatic degradation. 

Parenteral administration Absorption of medication following an intramuscular (IM) injection is often erratic in neonates owing to their small muscle mass and an inadequate perfusion of the IM site (81,82). In a study of infants and children aged 28 days to 6 years, the IM administration of chloramphenicol succinate produced serum levels that were not significantly different from those produced in intravenous (TV) administration (83). However, the bioavailability of most drugs administered intramuscularly has not been evaluated in the pediatric population. In addition to bioavailability issues, there are other concerns specific to pediatrics with the IM administration of drugs. The volume of solution injected is directly related to the degree of pain and discomfort associated with an IM injection. Manufacturers recommendations for reconstitution of IM products often... 

Dihydroergotamine is available for intranasal and parenteral administration by the intramuscular, subcutaneous, and intravenous routes " (see Table 59 ). Parenteral dihydroergotamine was viewed previously as inpatient or emergency department treatment for moderate to severe migraine, but patients can be trained to self-administer dihydroergotamine intramuscularly or subcutaneously. The bioavailability of dihydroergotamine is approximately 30% following intranasal administration, and maximum plasma concentration is achieved in 30 to 60 minutes." ... 

Using enteral feeding tubes to deliver drugs is a common practice. It offers an alternative to parenteral administration in patients unable to take drugs by the oral route. However, in addition to complications of tube occlusion, effects on drug bioavailability and other potential interactions need to be considered when using this route. Medications... 

Phosphorothioateoligonucleotidesare rap-idly and extensively absorbed after parenteral administration. For example, in rats, after an intradermal dose 3.6 mg/kg of C-ISIS 2105, a 120-mer phosphorothioate, approximately 70% of the dose was absorbed within 4 h and total temic bioavailability was in excess of 90% (200). After intradermal injection in humans, absorption of ISIS 2105 was similar to that observed in rats (201). Subcutaneous administration to rats and monkeys results in somewhat lower bioavailability and greater distribution to lymph nodes, as would be expected (202). 

The oral formulation, as absorption is poor and slow, as compared to the intranasal preparation, which is absorbed directly into nasal capillaries, or parenteral administration, which has a high bioavailability and fast onset. 

With most opioids, including morphine, the effect of a given dose is less after oral than after parenteral administration because of variable but significant first-pass metabolism in the liver. The bioavailability of oral preparations of morphine is -25%. The shape of the time-effect curve also varies with the route of administration, so the duration of action often is somewhat longer with the oral route. If adjustment is made for variability of first-pass metabolism and clearance, adequate relief of pain can be achieved with oral administration of morphine. Satisfactory analgesia in cancer patients is associated with a very broad range of steady-state concentrations of morphine in plasma (16-364 ng/mL). 

A classic technique employed in pharmacology and toxicology disposition studies for all routes of administration is the mass balance approach (Riviere, 1999). Mass balance analysis accounts for all of the topically applied dose of the compound, whether it is in the formulation, associated with the skin surface, penetrated into the stratum comeum, distributed into the carcass, or absorbed into and excreted from the blood into urine and feces. In this context, total recovery of 90% of the apphed dose is considered excellent recovery (Schaefer and Redelmeier, 1996). Mass balance studies are conducted by collecting all excreta after topical and parenteral administration. Data from a parenteral route such as intravenous dosing is required to correct for the fraction of absorbed compoimd appearing into the excreta collected if a precise estimate of bioavailability is to be determined and all routes of excretion are not collected (e.g., collection of urine and feces but not expired air) (Riviere, 1999). In such a study, absorption is calculated as follows ... 

C. As a polypeptide, it is bioavailable only by parenteral administration (intravenously or subcutaneously). Approximately 30% of octreotide is excreted unchanged in the urine, and it has an elimination half-life of 1.7 hours. Its half-life may be increased in patients with renal dysfunction and in the elderly. 

Dmg loading in micro- and nanoparticulate systems is generally carried out by one of two methods, i.e. during the preparation of particles (incorporation) or after their formation (incubation). The dmg delivery properties are also essentially dependent on the chemical and textural properties of the matrices, the porosity, wettability, erosion and the surface area. The matrix equally has an impact on the discharge profile for the bioavailability of the entrapped dmg. Nanoparticle-based delivery systems have the potential power to improve dmg stability, increase the duration of the therapeutic effect and permit enteral or parenteral administration, which may prevent or minimize dmg degradation and metabolism as well as cellular efflux [70, 71]. Protein nanoparticles can conveyance medications transversely across the blood-brain barrier that are not usually passed across after injection. A number of authors have demonstrated a considerable tendency for an accumulation of protein nanoparticles in certain tumours. The binding of a variety of cytotoxic dmgs, such as 5-fluorouracil,... 

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