Intramuscular administration pharmacokinetics

Madsen, S. M., Lindeburg, T., F01sgard, S., Jacobsen, E., and Sillesen, H. (1983) Pharmacokinetics of the gamma-aminobutyric acid agonist THIP (Gaboxadol) following intramuscular administration to man, with observations in dog. Acta Pharmacol. Toxicol. (Copenh.) 53, 353-357. 

Pharmacokinetics A mean elimination half-life of approximately 5 hours has been reported after intravenous doses of Roferon-A. Pharmacokinetic parameters are similar in healthy subjects and cancer patients after intramuscular doses. Dose-proportionate increases in serum levels occur with doses up to 198 MIU. The bioavailability of interferon alfa-2a after intramuscular administration is 80% to 83%, and its volume of distribution is 0.223 to 0.748 liter/kg. The total body clearance of interferon alfa-2a has been reported to range from 2.14 to 3.62ml/min per kg. 

Pharmacokinetics The elimination half-life of interferon alfa-2b after subcutaneous or intramuscular administration is 2 to 3 hours. 

Pharmacokinetics The absolute bioavailability of Humatrope after subcutaneous injection is about 75% absolute bioavailabUity is somewhat lower after intramuscular administration. According to label, the volume of distribution of somat-... 

Pharmacokinetics The absorption rate of Gonal-F following subcutaneous or intramuscular administration was found to be slower than the elimination rate. Hence the pharmacokinetics of Gonal-F are absorption rate-limited. After intravenous administration to pituitary down-regulated, healthy female volunteers, the serum profile of FSH appears to be described by a two-compartment open model with a distribution half-life of about 2 to 2.5 hours. Steady-state serum levels were reached after 4 to 5 days of daily administration. 

Pharmacokinetics Pegademase bovine is rapidly absorbed following intramuscular administration of Adagen, plasma adenosine deaminase activity generally normalizes after 2 to 3 weeks of weekly intramuscular injections. The half-life of pegademase is 48 to 72 hours. 

Pharmacokinetics Serum levels considered therapeutic (40pg/ml or greater) are achieved in most high-risk infants on intramuscular administration of the recommended dose. In studies in adult volunteers, palivizumab had a pharmacokinetic profile similar to a human IgGi antibody in regard to the volume of distribution and the half-life (mean 18 days). In pediatric patients less than 24 months of age, the mean half-life of palivizumab was 20 days. 

Results of pharmacokinetic studies of streptomycin are in most cases also applicable to dihydrostreptomycin and vice versa. In animals, the absorption of both streptomycin and dihydrostreptomycin is poor via the oral route but rapid after intramuscular administration. In cattle, peak serum levels were obtained 1 h after intramuscular injection of either streptomycin or dihydrostreptomycin (18), whereas serum concentrations produced in sheep and horses paralleled those obtained in cattle (19). As a result, most of an oral dose is recovered in the feces whereas most of a parenteral dose is recovered in the urine. However, if kidney function is severely impaired, little of an intramuscularly administered dose is excreted in the urine. 

Pharmacokinetic studies revealed rapid systemic absorption after intramuscular administration of dexamethasone, with peak plasma levels attained at 0.5 h and 6 h in dogs and rats, respectively. It is rapidly excreted in urine and feces. Its biotransformation profile is comparable in rats and humans and mainly involves hydroxylation to 6-hydroxy- and 2-dihydroxy-derivatives followed by conjuga-... 

Pharmacokinetic studies of intravenously administered indomethacin in cattle showed a wide extravascular distribution as suggested by the high volume of distribution and the long elimination half-life observed (99). Similar kinetic behavior of indomethacin was noticed after intramuscular administration in sheep (100). These results suggested that indomethacin could induce high residue levels in tissues. 

Pharmacokinetic properties Meptazinol has poor oral bioavailability due to extensive first-pass metabolism. Systemic availability is improved after rectal administration. Peak plasma concentrations are reached 30 min after rectal or intramuscular administration and plasma half-life is about 2 h. Plasma protein binding is low ( 30%). Meptazinole is extensively metabolized in the gut and liver mainly to the glucuronide derivative. Only about 10% is excreted unmetabolised in the faeces (Franklin, 1988). 

Pharmacokinetic properties Due to intensive first-pass metabolism, nalbuphine has a low oral bioavailability of less than 10%. After intramuscular administration peak plasma concentrations are reached after 30 min, half-life time is about 5 h. The compound is metabolized by glucuronidation and to a minor extent by N-dealkylation, and less than 10% is excreted unmetabolized (Lo et al., 1987). 

JM Delmas, AM Chapel, V Gaudin, P Sanders. Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration bioavailability and tissue residue studies. J Vet Pharmacol Ther 20 249-257, 1997. 

Wermeling DP, Miller JL, Archer SM, Manaligod JM, Rudy AC. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol 2001 41(11) 1225-31. 

Somani, S.M., Khalique, A. (1986). Distribution and pharmacokinetics of physotigmine in rat after intramuscular administration. Fundam. Appl. Toxicol. 6 327-34. 

The pharmacokinetic profile of HL6-7 was similar to that of HI-6. The mean absorption half-time of HL6-7 was about 14 min after intramuscular administration. Maximum HL6-7 concentration in plasma was reached after 30 min and the half-time of elimination was about 45 min (Eyer et al, 1992). 

Craigmill, A.L. Brown, S.A. Wetzlich, S.E. Gustafson, C.R. Arndt, T.S. Pharmacokinetics of ceftiofur and metabolites after single intravenous and intramuscular administration and multiple intramuscular administration of ceftiofur sodium to sheep. J. Vet. Pharmacol. Ther. 1997, 20, 139-144. 

Euller-Ziegler L, Velicitat P, Bluhmki E, Turck D, Scheuerer S, Combe B. Meloxicam a review of its pharmacokinetics, efficacy and tolerability following intramuscular administration. Inflamm Res 2001 50(Suppl l) S5-9. 

Delbeke F T, Debackere M, Desmet N et al 1986 Pharmacokinetics and diuretic effect of bumetanide foilowing intravenous and intramuscular administration to horses. Journal of Veterinary Pharmacology and Therapeutics 9 310-317... 

Vinagre, E., Rodrigue, C., San Andres, M.I., Boggio, J.C., San Andres, M.D. Encinas, T. (1998) Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration. Journal of Veterinary Pharmacology and Therapeutics, 21, 309-314. 

Wilson, W.D., Spensley, M.S., Baggot, J.D., Hietala, S.K. Pryor, P. (1991) Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration. Journal of Veterinary Pharmacology and Therapeutics, 14, 78-89. 

Budsberg, S.C., Kemp, D.T. Wolski, N. (1992) Pharmacokinetics of clindamycin phosphate in dogs after single intravenous and intramuscular administrations. American Journal of Veterinary Research, 53, 2333-2336. 

Woodard CL and Lukey BJ (1991). MMB-4 pharmacokinetics in rabbits after intravenous and intramuscular administration. Drug Metab Dispos, 19, 283-284. 

The last simulation will be to simulate the pharmacokinetics given by a different route of administration. For instance, suppose a central venous line could not be established in an elderly 50 kg female patient, which is not that uncommon an occurrence. A physician then asks whether they could give the dose by intramuscular injection and whether this would impact the drug s pharmacokinetics. To simulate the pharmacokinetics after intramuscular administration requires an absorption model, which is unknown. Some guesses can be made, however, after a review of the published literature. 

Jernigan, Hatch, and Wilson (1988) studied the pharmacokinetics of tobramycin after intramuscular administration in cats. Bioavailability was estimated at 102.5% with maximal concentrations occurring within about an hour. Hence, tobramycin absorption appears rapid and complete. There are few papers modeling the intramuscular absorption of drugs. Swabb et al. (1983) modeled the intramuscular administration of aztreonam, another antibiotic, in humans and found that a simple first-order absorption was adequate to explain the rapid (time to maximal concentrations was 0.88 h) and complete (101% bioavailability) absorption. Similarly, Krishna et al. (2001) also found that first-order absorption was sufficient to model the pharmacokinetics of quinine after intramuscular administration. In both cases, the drugs were formulated in water. 

The particular complexities of antibody pharmacokinetics and their relationship to pharmacodynamics have been thoroughly reviewed by Lobo and coworkers [16]. Many of the characteristics discussed above for macromolecules in general also apply in the case of antibodies. Thus, absorption following subcutaneous or intramuscular administration may be slow, with involvement of lymphatic transport, and attainment of peak blood concentrations may take days. Although absorption of antibodies from the gastrointestinal tract following oral administration to adult humans is very limited, absorption of IgG from the gastrointestinal tract of neonates of several species has been demonstrated [34]. This absorption occurs via interaction with the neonatal receptor for... 

Pepin, S., Lutsch, C., Grandgeorge, M., and Scherrmann, J.M. (1997) Snake F(ab )2 antivenom from hyperimmunized horse pharmacokinetics following intravenous and intramuscular administration in rabbits. Pharmaceutical Research, 12, 1470 1473. 

Vaishnaw, A.K., and TenHoor, C.N. (2002) Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. Journal of Pharmacokinetics and Pharmacodynamics, 29, 415 426. 

Somani, S.M. and Khalique, A., Pharmacokinetics and pharmacodynamics of physostigmine in the rat after intravenous administration, Drug Metab. Dispos., 15, 627, 1987. Somani, S.M. and Khalique, A., Distribution and pharmacokinetics of physostigmine in rat after intramuscular administration, Fundam. Appl. Toxicol, 6, 327, 1986. 

Kamo. J., Vinanen, R., Ii.sulo, E., Maenpaa, K., and Liukko, P, (1981). Placental iran.sfer and pharmacokinetics of atropine after a single maternal intravenous and intramuscular administration, Acta Aiiaesthe.slol. Scand. 25, 85-88. 

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