Repeated intravenous administration

One-compartment open model for repeated intravenous administration... 

The LMWHs appear to be as effective as unfractionated (mixed) heparins, but they offer certain advantages. For example, LMWHs can be administered by subcutaneous injection into fat tissues, thereby decreasing the need for repeated intravenous administration. Subcutaneous administration offers an easier and more convenient route, especially for people who are being treated at home or as outpatients.98 118 Dosing schedules of LMWHs are typically easier (once per day), compared to 2 or more daily injections of unfractioned heparin.132 The anticoagulant effects of LMWHs are also more predictable, and... 

Rats. Repeated intravenous administration of BZ to male albino rats was carried out for 20 dally Injections during a 4-wk period. The doses Included 0.01, 0.1, and 1.0 mg/kg. 

Thus far, most particulate administration has been restricted to infrequently dosed pharmaceuticals, such as phase contrast agents. Repeat intravenous administration of particulates is a young science which is expected to benefit from emerging particle engineering technologies. 

Figure 5 Time-course biood concentration of a xenobiotic foiiowing repeated intravenous administration (a) xenobiotic haif-iife shorter than the period of time between exposures (b) xenobiotic haif-iife ionger than the period of time between exposures.

Figure 9.22 Simulated concentration—time profile in a 50 kg patient after repeated intravenous administration (solid line) and intramuscular administration (dashed line) of 1 mg/kg every 8 h assuming the final model given in Eq. (9.17). Parameter values are given in Table 9.18. Absorption after intramuscular administration was modeled assuming first-order absorption with a rate constant of 1.2 per hour and complete bioavailability.

Fielding R M, Moon-McDermott L, Lewis R O, et al. (1999). Pharmacokinetics and urinary excretion of amikacin in low-clearance unilamellar liposomes after a single or repeated intravenous administration in the rhesus monkey. Antimicrob. Agents... 

Watkin DM (1957) Clinical, chemical, hematologic and anatomic changes accompanying repeated intravenous administration of fat emulsions to man. Metabolism [Suppl] 6 785-806... 

Notify a physician immediately. A suggested procedure for physicians or nurses is intravenous administration of 0.3 g (10 mL of a 3% solution) of sodium nitrite at the rate of 2.5 mL/min followed by 12.5 g (50 mL of a 25% solution) of sodium thiosulfate at the same rate. Watch the patient for 24 to 48 h, especially in cases of ingestion or skin absorption. If symptoms reappear, repeat the injections in half the original amounts. These solutions should be kept readily available. In some cases, first aid personnel have been trained to use the intravenous medication subject to government regulations. 

Dibutyltin dichloride induced acute pancreatitis and bile duct lesions in rats, depending on dose (6 and 8 mg/kg body weight intravenously) and time (1-24 weeks) (Merkord Hennighausen, 1989 Merkord et al., 1997, 1999 Sparmann et al., 2001). The lesions in the pancreas developed into a pancreatic fibrosis, and the lesions in the liver into liver cirrhosis. A single intravenous administration of dibutyltin dichloride at 4 mg/kg body weight induced a mild interstitial pancreatitis after 2 days (Merkord et al., 2001). Repeated administration of dibutyltin dichloride (4 mg/kg body weight intravenously) to rats at intervals of 3 weeks induced acute interstitial pancreatitis and, after 9-12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia) (Merkord et al, 2001). 

Previous reactors are at high risk for a new reaction. In many cases reported, re-administration of the culprit contrast medium to patients with a previous non-immediate exanthema resulted in a repeat reaction [1]. In some (but not all) cases, a more severe reaction with subsequent RCM exposure has been described. After provocation tests, a re-appearance of the exanthemas after intravenous administration of the culprit contrast medium has been reported in patients with previous contrast medium-induced eruptions [1]. 

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

Wallace D., Mactutus C., Booze R. Repeated intravenous cocaine administrations locomotor activity and dopamine D2/D3 receptors. Synapse. 19, 1996. 

Medical Management Immediate decontamination after exposure is the only way to prevent damage to victims, followed by symptomatic management of lesions. Hospital care tends to be supportive. It should be repeated that liquid arsenical vesicants produce more serious lesions on dermal surfaces than do liquid mustard. In toxic victims, liberal fluids by mouth or intravenous, and high-vitamin, high-protein, high-carbohydrate diets could be indicated. For those victims where shock is in evidence, provide the usual supportive measures such as intravenous administration, blood transfusions, or other vascular volume expanders should be indicated. 

After intravenous administration, dihydroergotoxine aikaioids show maximai uptake in viscerai organs (10-5 M) and the centrai nervous system (10-7 M), and concentrations increase with repeated administration (Iwangoff et ai. 1978). Maximai piasma concentrations of ergoioids occur approximateiy 2 hours after orai administration (Aeiiig and Nuesch 1977). Eiimination haif-iife varies from 1.4 to 6.2 hours for the aipha phase and from 13 to 50 hours for the beta phase. 

Harrod et al. (2004) studied DA transporters and Dl, D2, and D3 receptors following repeated intravenous nicotine administration in male and female rats. No sex differences were depicted in the number of Dl or D2 receptors in either the striatum or the NAC, but female rats had increased number of DA transporters in both the core and shell of the NAC and decreased density of D3 receptors in the shell of NAC, compared to males. Nicotine-induced changes of DA transporters and D3 receptors are reported to be partly responsible for increased behavioral sensitization measured by locomotor activity in female rats. 

Booze et al. (1999) have shown that while repeated intravenous nicotine administration induced behavioral sensitization in male and female rats, female rats exhibited increased sensitivity to repeated nicotine, relative to males. Furthermore, repeated nicotine administration did not interfere with intact female vaginal cytology, or produce persistent vaginal estrus, esttus acyclicity, or changes in body weight. The peak arterial nicotine concentrations were similar in male and female rats. 

Blaha V, Yang ZJ, et al (1998) Systemic nicotine administration suppresses food intake via reduced meal sizes in both male and female rats. Acta Medica41(4) 167-173 Blanchard BA, Steindorf S, et al (1993) Sex differences in ethanol-induced dopamine release in nucleus accumbens and in ethanol consumption in rats. Alcohol Cfin Exp Res 17(5) 968-973 Booze RM, Welch MA, et al (1999) Behavioral sensitization following repeated intravenous nicotine administration gender differences and gonadal hormones. Pharmacol Biochem Behav 64(4) 827-839... 

Administration of nickel carbonyl to rats by repeated intravenous injection was associated with an increased incidence of various malignant tumors. Inhalation exposure of rats was associated with a few pulmonary malignancies not reaching statistical significance. 

Combinations of amphotericin-B with flucytosine are sometimes used to reduce the occurrence of resistance. Amphotericin-B is not absorbed from the gastrointestinal tract which necessitates intravenous administration. It is 90% protein bound and widely distributed, except for the CNS. For the treatment of fungal meningitis therefore only intrathecal drug administrations can be effective. Amphotericin-B is eliminated very slowly in urine, mainly in an inactive form, with an elimination half-life of about 24 hours which can increase to up to 15 days with repeated doses. 

Depressed patients, when compared with nondepressed control subjects, have been shown repeatedly to have an earlier occurrence of REM sleep onset induced by intravenous administration of cholinomimetics (M. Berger and Riemann 1993 Gillin et al. 1991 Riemann et al. 1994 Sitaram et al. 1980]. This well-established supersensitive response to cholinomimetics, however, also has been observed in schizophrenic patients (M. Berger and Riemann 1993 Riemann et al. 1991]. Yet, an increase in the density of rapid eye movements through cholinergic stimulation appears to be specific to depression [Riemann et al. 1994]. 

Intramuscular injection of carboprost tromethamine can also be used to induce abortion. Unlike the one-time intrauterine instillation of dinoprost, carboprost is given repeatedly up to the total dose of 2.6 mg normally required to cause abortion. Intra-amniotic administration has close to a 100% success rate, with fewer and less severe adverse effects than intravenous administration. 

Studies of omalizumab in asthmatic volunteers showed that its administration over 10 weeks lowered plasma IgE to undetectable levels and significantly reduced the magnitude of both the early and the late bronchospastic responses to antigen challenge. Clinical trials have shown repeated intravenous or subcutaneous injection of anti-IgE MAb to lessen asthma severity and reduce the corticosteroid requirement in patients with moderate to severe disease, especially those with a clear environmental antigen precipitating factor, and to improve nasal and conjunctival symptoms in patients with perennial or seasonal allergic rhinitis. 

The treatment of acute attacks of asthma in patients reporting to the hospital requires more continuous assessment and repeated objective measurement of lung function. For patients with mild attacks, inhalation of a -receptor agonist is as effective as subcutaneous injection of epinephrine. Both of these treatments are more effective than intravenous administration of aminophylline. 

---