Bioavailability intramuscular injection

Most parenteral cephalosporins have good bioavailability after intramuscular injection, and a few members of each cephalosporin generation have good oral bioavaU-abUity (Table 45.2). The ester prodrugs cefuroxime ax-etil (Ceftin) and cefpodoxime proxetil (Vantin) are oral... 

When utilized as sedative hypnotics, barbiturates are administered orally. They are rapidly and completely absorbed by this route with nearly 100% bioavailability and an onset of action ranging from 10 to 60 min.3 Sodium salts are more rapidly absorbed than free acids. Intramuscular injections of sodium salts should be made deep into the muscle to prevent pain and tissue damage. Some barbiturates are also administered rectally barbiturates utilized for the induction and maintenance of anesthesia (thiopental) or for treating status epilepticus (phenobarbital) are administered intravenously. 

The rates of oral absorption of benzodiazepines differ depending on a number of factors, including lipophilicity. Oral absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Oxazepam, lorazepam, and temazepam are absorbed from the gut at slower rates than other benzodiazepines. The bioavailability of several benzodiazepines, including chlordiazepoxide and diazepam, may be unreliable after intramuscular injection. Most of the barbiturates and other older sedative-hypnotics are absorbed rapidly into the blood following their oral administration. 

These compounds have high bioavailability after intramuscular administration and tend to concentrate in synovial membranes, liver, kidney, spleen, lymph nodes, and bone marrow. One month after an intramuscular injection, 75-80% of the drug is eliminated from the serum, but intramuscular gold s total body half-life is approximately 1 year. Auranofin is only about 25% bioavailable. Gold compounds are excreted approximately 66% in the urine and 33% via the feces. There has generally been no correlation found between serum gold concentration and either efficacy or toxicity. 

Table 2 offers a summary of clinical parameters for several representative ER modulators, showcasing similarities and differences across scaffolds. Thus the benzothiophene molecule raloxifene (1) and both TPEs tamoxifen (4) and toremifene (6) provide oral bioavailability, while the steroid-like molecule fulvestrant (9) requires administration via intramuscular injection. On the other hand, all three oral treatments require daily dosing, in contrast with monthly administration for the injectable, consistent with the relative values of elimination half-life. 

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... 

Disposition in the Body. Readily absorbed after oral administration bioavailability about 55%. Flupenthixol decanoate is very slowly absorbed from the site of intramuscular injection. Peak plasma concentrations are attained about 3 to 6 hours after oral administration and 3 to 7 days after intramuscular injection. The main metabolic reactions are sulphoxidation, side-chain N-dealkylation and glucuronic acid conjugation. AT-Desalkylflupen-thixol and flupenthixol sulphoxide are the major metabolites found in plasma (both are inactive). Numerous metabolites are excreted in the urine and faeces and there is evidence of enterohepatic circulation. 

The plasma concentration profiles can vary widely among different parenteral preparations of the same drug administered by intramuscular injection, even when the same injection site is used. Comparison of the plasma concentration profiles obtained after intramuscular injection in the lateral neck of ruminant calves of five different parenteral preparations of ampi-cillin at a similar dose level (7.7 l.Omg/kg) serves to illustrate the variation that can exist among preparations (Fig. 5). Estimation of the bioavailability of each preparation relative to a reference preparation... 

Flaloperidol is well absorbed orally with a bioavailability of 60-65% due to first-pass hepatic metabolism. It has a reversible oxidation/reduction metabolic pathway it is metabolized via reduction to reduced haloperidol, which is biologically inactive. Both agents are rapidly absorbed after intramuscular injection, peaking within 10 min. Butyrophenones are metabolized in the liver to inactive metabolites. Concentrations of butyrophenones are found in the liver, central nervous system, and throughout the body. Flaloperidol is 92% protein bound. Haloperidol is 15% eliminated through the bile. The elimination half-life is 14-41 h. The half-life of droperidol is 2 h 10% is recovered unchanged in the urine. 

Loxapine is readily but incompletely absorbed. Due to first-pass metabolism, oral bioavailability is 30% less than bioavailability after intramuscular injection. Peak blood levels occur 1 or 2h after oral administration and 5 h after intramuscular injection. Loxapine is extensively metabolized in the liver through aromatic hydroxylation, N-demethylation, or N-oxidation. The metabolite amoxapine is active and marketed as an antidepressant. Loxapine is widely distributed throughout the body, including the central nervous system. The main metabolites are excreted both in the urine and feces, and 50% of a... 

The extent of absorption (systemic availability) of a drug is estimated by the method of corresponding areas. Comparison of total AUC following the intramuscular injection of a parenteral preparation (solution or suspension) with that following the intravenous injection of a bolus dose of the drug (parenteral solution) provides an estimation of absolute bioavailability, while comparison of AUCs following intramuscular injection of different parenteral preparations (one of which must be a reference formulation) at the same injection site or of the same parenteral preparation at different injection sites estimates the relative bioavailability. A crossover design with an appropriate washout period between the phases of the bioavailability study should be used whenever feasible. 

The intramuscular bioavailability of amoxycillin in pigs is 83%, based on intravenous injection of amoxycillin sodium and intramuscular injection of amoxycillin trihydrate 15% in oil (described as the conventional formulation) in the neck, 10 cm behind the ear, of pigs. The conventional formulation provides slow absorption of amoxycillin (MAT, 7.3 h), Cmax of 5.1 pg/mL and delays elimination of the drug (MRT .m. is 8.8 h compared with MRT .V. of 1.5 h). Administration of the long-acting formulation of amoxycillin trihydrate 15% in... 

Fig. 2.8 Effect of species and weight on the bioavailability of amoxycillin after intramuscular injection of amoxycillin trihydrate aqueous suspension (100mg/mL) at the same dose (7 mg/ kg) in the various species except cats (10-12mg/kg).

Phenytoin. Phenytoin (l s slowly absorbed from the small intestine. The rate, extent, and bioavailability vary because of the manufacturer s formulation process. Intramuscular injection tends to precipitate at the site of injection, resulting in erratic plasma levels these levels are significantly lower than those obtained by the oral route. Phenytoin is metabolized in the liver to inactive hydroxylated metabolites (see Fig. 6.3) (20). For a complete discussion, the reader is referred to the earlier edition of this chapter (8).The metabolism of phenytoin is capacity limited and shows satu-rability. Because the elimination of the p-hy-dro glucuronide metabolite is rate limited by its formation from phenytoin, measure-... 

Residues at the site of injection present specific problems. The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle. Chloramphenicol, tylosin, penicillins, dihydrostreptomycin and oxytetracycline have been shown to produce local irritation at the site of injection leading to residues persistence and this may be exacerbated by the solvent used (47-49) with one oxytetracycline product which produced little irritation, residues did not persist (49). Large variations in pharmacokinetic behaviour were noted in addition to the persistence at the injection site and in particular with oxytetracycline, bioavailability was reduced. These studies demonstrate the usefulness of pharmacokinetic data when studying specific routes of administration, and in particular they demonstrate the need to take into account other biological phenomena when attributing withdrawal periods, in this case, irritation at the injection site. The new draft EC Guideline requires that injection sites are examined in residues studies with injectable products and in the case of persistence at the site, then the withdrawal period will be based on this. 

Testosterone itself, although it is absorbed on oral administration, is ineffective because of poor bioavailability (i.e., rapid first-pass hepatic metabolism). Even the tl/2 of injected testosterone from an oil solution is only about 4-10 minutes. The several esters listed in Table 14-8—acetate, propionate, cypionate, and enanthate—on intramuscular injection of oil solutions, allows for infrequent doses (e.g., every 2 weeks) because of relatively slow absorption and subsequent hydrolysis of these pro-drugs to the parent compound—testosterone. In a practical sense, then, these esters are more active. 

Intramuscular injection (i.m.) Insulin for diabetes Usually high bioavailability Discomfort to patient... 

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