Intravenous administration route cocaine

Perez-Reyes et al.8 estimated that only 32% of a dose of cocaine base placed in a pipe is actually inhaled by the smoker. Cone9 compared the pharmacokinetics and pharmacodynamics of cocaine by the intravenous, intranasal, and smoked routes of administration in the same subjects. Venous plasma cocaine concentrations peaked within 5 min by the intravenous and smoked routes. Estimated peak cocaine concentrations ranged from 98 to 349 ng/ml and 154 to 345 ng/ml after intravenous administration of 25-mg cocaine hydrochloride and 42-mg cocaine base by the smoked route, respectively. After dosing by the intranasal route (32 mg cocaine hydrochloride) estimated peak plasma cocaine concentrations ranged from 40 to 88 ng/ml after 0.39 to 0.85 h.9 In this study, the average bioavailability of cocaine was 70.1% by the smoked route and 93.7% by the intranasal route. Jenkins et al.10 described the correlation between pharmacological effects and plasma cocaine concentrations in seven volunteers after they had smoked 10 to 40 mg cocaine. The mean plasma... 

A two-compartment open linear model has been described for the pharmacokinetic profile of cocaine after intravenous administration.14 The distribution phase after cocaine administration is rapid and the elimination half-life estimated as 31 to 82 min.14 Cone9 fitted data to a two-compartment model with bolus input and first-order elimination for the intravenous and smoked routes. For the intranasal route, data were fitted to a two-compartment model with first-order absorption and first-order elimination. The average elimination half-life (tx 2 3) was 244 min after intravenous administration, 272 min after smoked administration, and 299 min after intranasal administration. 

Hence, intravenous data were modeled first, followed by inhalational, then intranasal. Once the pharmacokinetics of each individual route of administration was established, all model parameters were then estimated simultaneously. Initial values for cocaine pharmacokinetics after intravenous administration were estimated using noncompartmental methods. Total systemic clearance was estimated at 100 L/h and volume of distribution at steady-state was estimated at 232 L. Central compartment clearance and intercompartmental clearance were set equal to one-half total systemic clearance (50 L/h), whereas central and peripheral compartment volumes were set equal to one-half volume of distribution (116 L). Data were weighed using a constant coefficient of variation error model based on model-predicted plasma concentrations. All models were fit using SAAM II (SAAM Institute, Seattle, WA). An Information-Theoretic approach was used for model selection, i.e., model selection was based on the AIC. 

Cocaine acts as a potent local anesthetic and is a strong CNS stimulant it extends and intensifies the effects of dopamine, norepinephrine, serotonin neurotransmitters [3], The effects of cocaine can vary in relation to the individual characteristics, the administered dose, frequency of use, and route of administration. The intranasal administration causes plasma peak concentrations after 5-20 min, the euphoric effect in 15-20 min with a half-life of 40 min. The oral route involves a slow and low absorption with plasma peak concentrations after approximately 90 min and euphoric effect in 15-20 min. Intravenous plasma peak is immediate, euphoric effect occurs after 4-8 min with a half-life of about 40 min. Finally it may be administered through inhalation of combustion products or crack vapors, with great absorption speed. 

For recreational use, cocaine (hydrochloride salt) is often administered by nasal insufflation ( snorting ) or less frequently, intravenously. Cocaine is more volatile when converted from the salt to the freebase therefore freebase cocaine may be inhaled by smoking. This latter route of administration results in a rapid onset of action. It has gained increased popularity owing to the ready availabihty of the freebase cocaine form known as crack. Consequently the number of emergency room admissions related to cocaine toxicity has increased. 

Small molecules such as cocaine and cephalexin can be transported directly to the CNS from the nasal cavity.24 25 Sakane and colleagues25 reported that cephalexin preferentially entered the CSF after nasal administration compared to intravenous (IV) and intraduodenal administration in rats. The levels of cephalexin in CSF were 166-fold higher 15 minutes after nasal administration than those of the other two routes. Most recently, studies by Wang and colleagues showed that the ratio of the methotrexate AUCcsp value between the IN route and the IV injection was over 13-fold.26... 

Cocaine is a notorious drug of abuse that is administered via a number of routes of administration, including intranasal (snorting), intravenous, and inhalational... 

Table 5.8 Cocaine plasma concentrations (ng/mL) after intravenous, intranasal, and inhalational routes of administration as reported by Jeffcoat et al. (1989). ...

Smoking is another fast route of administration. Its quick delivery may be why smoking can be such a seductive prospect for many users, whether the drug of choice is nicotine or crack cocaine. It is obvious that the potential for addiction is much greater when a highly addictive drug can be taken in convenient fashion. Many professionals consider the immediate reinforcement of intravenous injection and oral filtration a major contribut-... 

A number of reports in the mid to late 1980 s described patients who developed rhabdomyolysis while using cocaine [118-120]. Some of these patients experienced acute renal failure [121-125]. While the exact incidence of acute renal failure secondary to cocaine rhabdomyolysis is unknown, in one reported series it occurred in only three of 211 admissions for cocaine related complications [114]. On the other hand, in another series of nearly 40 patients the incidence of cocaine related acute rhabdomyolysis increased over the period of enrollment from 2 patients in 1985 to 22 patients in 1987 [126]. Several reports of patients with cocaine-induced rhabdomyolysis have clearly defined both the clinical syndrome and the risk factors for the development of acute renal failure and an adverse outcome [123, 126, 127]. Most patients have been previously healthy young males (mean age 30-35 years old and 80-85% male). The cocaine has been smoked, used intravenously, snorted, or taken orally implying that route of administration was not relevant [122,123,126, 127]. In contrast to narcotic related rhabdomyolysis, a history of prolonged coma or stupor is absent. On presentation, the majority of patients are combative and... 

Cocaine is active via nearly every possible route of administration however, insufflation of snow or coke represents one of the most popular routes. Administered in this manner, peak effects and plasma levels are achieved within 30 minutes (48). Smoking the freebase form of cocaine ( crack ) results in an even more rapid effect. The freebase form rather than the hydrochloride salt is used for smoking, because the temperatures required for vaporization of the salt result in considerable decomposition (48). Intravenously administered cocaine can achieve peak blood levels within a few minutes. Cocaine is metabolized to benzoylecgonine, the methyl ester of eegonine, and to a lesser extent, to eegonine, norcocaine, and hydroxylated derivatives. 

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