Subcutaneous administration

Reaction of estrone with a metal acetylide affords 17a-ethynyl-173-hydroxy-estradiol (etbynylestradiol, 30a EE). This compound is equipotent with estradiol by subcutaneous administration, but it is 15 to 20 times as active when administered orally. Ethynylation of the methyl ether of estradiol analogously affords mestranol (30b), It should be noted that the same factors apply in these reactions as in previously discussed reductions at 17 almost the sole products of these reactions are those which result from attack of reagent from the least hindered a side of the steroid. Ethynylestradiol and mestranol are of special commercial significance since the majority of the oral contraceptives now on sale incorporate one or the other of the compounds as the estrogenic component. 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin liposomes, Diabetes, 31. 506-511. 

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

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Use of the first-generation somatostatin analog octreotide is limited by its extremely short duration of action and requirement for subcutaneous administration at least three times a day. If a patient s GH level returns to baseline before the end of an 8-hour dosing interval, the frequency of octreotide administration can be increased to every 4 to 6 hours. Most patients require octreotide in doses of 100 to 200 meg three times daily.19,20 To improve patient tolerance to gastrointestinal (GI) adverse effects, start octreotide at 50 meg every 8 hours.20 Assess IGF-I serum concentrations every 2 weeks after initiating therapy to further titrate dose in increments of 50 meg per dose. 

Carrington CD, Burt CT, Abou-Donia MB. 1988. In vivo 3 IP nuclear magnetic resonance studies on the absorption triphenyl phosphate and tri-ort/zo-cresyl phosphate following subcutaneous administration in hens. Drug Metab Distrib 104-109. 

In order to explore the importance of the H3 receptor in sleep-wakefulness, Toyota et al. (2002) compared the wake-promoting effects of the H3 receptor antagonist thioperamide in wild-type and H3 receptor KO mice. In wild-type mice, subcutaneous administration of thioperamide (10 mg/kg) increased wakefulness with a concomitant decrease in NREM sleep during the first 2 h after administration at lights-on. REM sleep was unaffected. In contrast, thioperamide had no effect on sleep-wakefulness in H3 receptor KO mice (Toyota et al., 2002). 

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. 

Figure 2 Mean plasma (Cp), CSF (CCSF), and brain (Cb) compound concentration-time profiles (graph) and matrix-specific neuropharmacokinetic parameters (table) of a compound in rats following subcutaneous administration [42]. Abbreviations Cmax, maximal compound concentration Tmax, time of Cmax tV2, compound half-life.

The answer is a. (Hardman, p 224.) Epinephrine is the drug of choice to relieve the symptoms of an acute, systemic, immediate hypersensitivity reaction to an allergen (anaphylactic shock). Subcutaneous administration of a 1 1000 solution of epinephrine rapidly relieves itching and urticaria, and this may save the life of the patient when laryngeal edema and bronchospasm threaten suffocation and severe hypotension and cardiac arrhythmias become life-endangering. Norepinephrine, isoproterenol, and atropine are ineffective therapies Angioedema is responsive to antihis-... 

The germanium derivative of cysteine Ge[SCH2CH(NH2)COOH]4 shows low toxicity in acute (3402 mg kg-1), subacute and chronic experiments53. No teratogenic effects were noticed in rats and mice after subcutaneous administration of the compound54. 

The intranasal dose is 200 units daily, alternating nares every other day. Subcutaneous administration of 100 units daily is available but rarely used because of adverse effects and cost. 

Subcutaneous administration of -hexanc at 143 mg/kg/day for 30 days has been reported to decrease the threshold for ventricular fibrillation in perfused hearts from male Wistar rats (Khedun et al. 1996). Myocardial magnesium and potassium levels were reduced in treated rats. When these levels were corrected by supplementation, the ventricular fibrillation potential was still reduced. Histological alterations (disordered myocardial Z-bands) were also observed in exposed rats. 

In animals, several studies suggest a variable toxicity of phenol depending on age. Deichmann and Witherup (1944) compared the response to oral and subcutaneous administration of phenol in 3 age groups of rats 10 days old, 5 weeks old, and adults. At a dose of 600 mg/kg orally, death occurred in 90% of 10-day-old rats, in 30% of 5-week-old rats, and in 60% of adult rats. Similarly, 3,000 mg/kg... 

These three analogues are more metabolically stable than LHRH. Thus, the half-life of nafarelin in monkeys and rats after i.v. administration was four to five times longer than that of LHRH [214], When incubated in monkey plasma, LHRH was readily degraded (f1/2 ca. 2 h), whereas nafarelin was more resistant (tm> 160 h). The metabolism of [14C]nafarelin was also investigated in humans following subcutaneous administration [215]. As shown in Fig. 6.39, the first metabolic steps were cleavage in the 4-5, 5-6, and 7-8 positions. Because of the presence of the 14C-label, the fate of D-2-Nal could be carefully monitored. The same metabolic pattern was observed in the rhesus monkey [216]. 

The route of administration of an NCE is typically the intended clinical route of administration. However, an alternative route may be used if this leads to an increase in systemic exposure of parent drug or major metabolites or if this alternative route satisfies another important objective of the study. For example, it is common to increase the exposure following inhalation administration by associating a subcutaneous administration of the NCE. 

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