Subcutaneous drug administration pharmacokinetics

Various characteristics of the molecule influence its chances of reaching its target receptor since they influence the nature and extent of the body s effect on it. A drug s pharmacokinetic profile therefore determines the extent of the drug s opportunity to exert its pharmacodynamic effect. While there are various routes for human drug administration (oral rectal intravenous, subcutaneous, intramuscular, and intra-arterial injections topical and direct inhalation into the lungs), the most common for small-molecule drugs is oral administration, and discussions in the first part of this chapter therefore focus on oral administration. (In contrast, biopharmaceuticals are typically administered by injection, often directly into the bloodstream.)... 

On the other hand, polycyclic aromatic compounds given orally or subcutaneously are more likely to cause aplastic anemia, leukemia, and lymphatic tumors in Ah-nonresponsive mice. These effects are manifest in tissues distant from the site of drug administration. In the example of oral benzo[a]pyrene, pharmacokinetic studies have shown a 10-and 20-fold higher uptake in the marrow and spleen of Ah-nonresponsive than of Ah-responsive mice this confirms the phenomenon called "first-pass elimination kinetics."... 

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. 

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). 

Zifrosilone (18) is a novel tight-binding inhibitor of acetylcholinesterase, which is in development as a potential therapeutic compound in the symptomatic treatment of Alzheimer s disease [72]. Pharmacokinetics and pharmacodynamics of the compound were studied in the dogs and rats after single intravenous and subcutaneous administrations. When evaluated in human healthy volunteers, the orally administered drug was well tolerated but displayed a strong dose-related inhibition of red blood cell acetylcholinesterase [73] and its development was consequently halted. 

Substantial progress has also been reported with regard to the synthesis and testing of nuclease-resistant ribozyme drugs. Modifications including phosphorothioates and nucleoside analogs have been demonstrated to be incorporable in many sites in hammerhead ribozymes, to increase nuclease resistance and support retained ribozyme activity (59-61). In fact, modified relatively nuclease-resistant ribozymes were reported to decrease the target, stromelysin, mRNA levels in knee joints of rabbits after intra-articular injection (62). Further, the pharmacokinetics of a relatively nuclease-stable hammerhead ribozyme were determined after intravenous (i.v.), subcutaneous (s.c.), or intraperitoneal (i.p.) administration to mice. The ribozyme... 

The most widely used parenteral administration avenues are intravenous (iv), intramuscular (im), and subcutaneous (sc). In addition, there are several minor applications (e.g. intraarterial). Application of a protein drug by the different main parenteral administration routes may have profound effects on the pharmacological performances. When the drug is administered iv, it is immediately available for action in the circulation, while drugs administered im or sc need more time to reach the blood (depot effect), and consequently the pharmacokinetic (PK) profiles could be different. Besides the PK, the route of administration may have influence on the primary distribution of the drug. For example, when administered sc, smaller and hydrophiUic proteins tend to enter the venous system, while larger and/or more hydrophobic proteins tend to... 

The terminal half-life of erythromycin A in calves and adult cows is relatively short (2.9-4.1 h) after intravenous administration, but much longer after intramuscular (11.9 h) or subcutaneous (18.3 to 26.9 h) dosing, as a consequence of flip-flop pharmacokinetics of commercially available formulations, that is, of a very slow process of drug... 

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