Subcutaneous administration pharmacokinetics

Intravenous administration displays a different pharmacokinetic profile than subcutaneous administration... 

Yoshimura et al. [132] studied the pharmacokinetics of primaquine in calves of 180—300 kg live weight. The drug was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously or subcutaneously and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high performance liquid chromatography. The extrapolated concentration of primaquine at zero time after the intravenous administration was 0.5 0.48 pg/mL which decreased with an elimination half-life of 0.16 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.5 0.08 pg/mL at 1.67 0.15 h after intravenous administration. The corresponding value was 0.47 0.07 pg/mL at 5.05 1.2 h after subcutaneous administration. The elimination half-lives of carboxyprimaquine after intravenous and subcutaneous administration were 15.06 0.99 h and 12.26 3.6 h, respectively. 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

Ebert U, Siepmann M, Oertel R, Wesnes KA, Kirch W. (1998). Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. J Clin Pharmacol. 38(8) 720-26. 

Pharmacokinetics Epoetin alfa IV is eliminated via first-order kinetics with a circulating half-life of 4 to 13 hours in patients with CRF. Within the therapeutic dosage range, detectable levels of plasma erythropoietin are maintained for at least 24 hours. After subcutaneous administration of epoetin alfa to patients with CRF,... 

Do not substitute subcutaneous administration of/Avonex for IM administration. Subcutaneous and IM administration have been observed to have nonequivalent pharmacokinetic and pharmacodynamic parameters. 

Pharmacokinetics The absolute bioavailability after a 70 mg subcutaneous bolus injection in healthy subjects (n = 11) is 95%. In subjects with RA, maximum plasma concentrations occurred 3 to 7 hours after subcutaneous administration of anakinra at clinically relevant doses (1 to 2 mg/kg n = 18) the terminal half-life ranged from 4 to 6 hours. In RA patients, no unexpected accumulation was observed after daily subcutaneous doses for up to 24 weeks. The estimated clearance increased with increasing Ccr and body weight. 

Vlasuk GP, Bradbury A, Lopes-Kinninger L, Colon S, Bergum PW, Maki S, Rote WE. Pharmacokinetics and anticoagulant properties of the factor Vila - tissue factor inhibitor recombinant nematode anticoagulant protein c2 following subcutaneous administration in man dependence on the stoichiometric binding to circulating factor X. Thromb Haemost 2003 90 803-12. 

Pharmacokinetics Well absorbed after subcutaneous administration. Half-life 48.5 hr. 

Pharmacokinetics Well absorbed after subcutaneous administration. Following administration, an increase in reticulocyte count occurs within 10 days, and increases in Hgb, Hct, and RBC count are seen within 2-6 wk. Half-life 4-13 hr. 

Mechanism of Action Aprotein that binds to tumor necrosis factor (TNF), blocking its interaction with cell surface receptors. Elevated levels of TNF, which is involved in inflammatory and immune responses, are found in the synovial fluid of rheumatoid arthritis patients. Therapeutic Effect Relieves symptoms of rheumatoid arthritis. Pharmacokinetics Well absorbed after subcutaneous administration. Half-life 115 hr. 

Pharmacokinetics Well absorbed after subcutaneous administration. Undergoes minimal, if any, metabolism. Highly bound to antithrombin 111. Distributed mainly in blood and to a minor extent in extra vascular fluid. Excreted unchanged in urine. Removed by hemodialysis. Haif-Hfe 17-21 hr (prolonged in patients with impaired renal... 

Pharmacokinetics Well absorbed following subcutaneous administration. Protein binding Very high. Metabolized in the liver. Removed from the circulation via uptake by the reticuloendothelial system. Primarily excreted in urine. Not removedby hemodialysis. Half-life i-6hr. 

Mechanism of Action A biologic response modifier that induces activation of macrophages in blood monocytes to phagocytes, which is necessary in the body s cellular immune response to intracellular and extracellular pathogens. Enhances phagocytic function and antimicrobial activity of monocytes Therapeutic Effect Decreases signs and symptoms of serious infections in chronic granulomatous disease. Pharmacokinetics Slowly absorbed after subcutaneous administration. Half-life 0.5-1 hr. 

Pharmacokinetics Readily absorbed from the GI tract (duodenum) after IM or subcutaneous administration. Metabolized in the liver. Excreted in urine eliminated by biliary system. Onset of action with PO form, 6-10 hr with parenteral form, hemorrhage controlled in 3-6 brand PT returns to normal in 12-14 hr. 

Mechanism of Action A monoclonal antibody that selectively binds to human immunoglobulin E (IgE) preventing it from binding to the surface of mast cells and basophils. Therapeutic Effect Prevents or reduces the number of asthmatic attacks. Pharmacokinetics Absorbed slowly after subcutaneous administration, with peak concentration in 7-8 days. Excreted in the liver, reticuloendothelial system, and endothelial cells. Half-life 26 days. 

Pharmacokinetics Readilyabsorbed after subcutaneous administration. Excreted by the kidneys. Half-life 80 hr. 

Pharmacokinetics According to product label, analysis of data from a study in healthy men and women who received intravenous and subcutaneous Neumega revealed that following subcutaneous administration absorption is the rate-limiting step. Hence the elimination rate constants... 

The pharmacokinetics of ivermectin differ with the animal species, formulation, and the route of administration (50). When goats were given a subcutaneous administration of 0.2 mg ivermectin /kg bw, the mean concentrations of ivermectin in plasma and milk increased initially to reach at 2.8 day the maximum levels of 6.12 and 7.26 ppb, respectively (51). The drug could be detected in milk for 25 days postdosing, the total drug amount recovered over this period being estimated at 0.6% of the administered dose. This percentage is low compared with the 4% level determined in sheep (52) and 5.6% in cows (53). 

Pharmacokinetic data after intravenous, intraruminal, or subcutaneous administration of 0.25-0.5 mg flumethasone/kg bw/day for 8 days in sheep showed that maximum plasma levels were reached within 48 h postdosing. The metabolic clearance was estimated at about one-quarter to three-quarters of that found for cortisol in sheep. 

Phillips, J.A., Craig, S.J., Bayley, D., Christian, R.A., Geary, R. and Nicklin, P.L. (1997) Pharmacokinetics, metabolism, and elimination of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A) after intravenous and subcutaneous administration. Biochem. Pharmacol, 54, 657-668. 

Fig. 4.12 Pharmacokinetic/pharmacodynamic relationship of ISIS 22023 in mouse plasma with liver Fas mRNA reduction following subcutaneous administration of a single dose (50 mg/kg). Symbols represent observed concentrations or Fas mRNA levels (error bars represent standard deviation for ISIS 22023 concentrations, or standard error for Fas mRNA levels n = 3). Solid lines represent predicted ISIS 22023 concentrations in plasma or Fas mRNA levels using nonlinear regression.

Fig. 12.6 (A) Predicted serum concentrationtime profiles for etanercept following subcutaneous administration of the low (25 mg once weekly), medium (25 mg twice weekly), and high (50 mg twice weekly) dose in rheumatoid arthritis patients using the population pharmacokinetic model described previously...

Bara L, Billaud E, Gramond G, etal. Comparative pharmacokinetics of a low molecular weight heparin (PK 10 169) and unfractionated heparin after intravenous and subcutaneous administration, Thromb Res 1985 39 631-636. 

Verhagen, A. Ebels, J.T. Dogterom, A.A. Jonkman, J.H. Pharmacokinetics and pharmacodynamics of a single dose of recombinant human growth hormone after subcutaneous administration by jet-injection comparison with conventional needle-injection. Eur. J. Clin. Pharmacol. 1995, 49 (1-2), 69-72. 

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