Intranasal and oral cocaine kinetics

  title={Intranasal and oral cocaine kinetics},
  author={Paul K. Wilkinson and Craig Van Dyke and Peter I. Jatlow and Paul Barash and Robert Byck},
  journal={Clinical Pharmacology \& Therapeutics},
Plasma cocaine levels were determined in 7 subjects after intranasal and oral cocaine. Intranasal doses of 0.19, 0.38, 0.75, 1.5, and 2.0 mg/kg were given as a 10% aqueous solution; 0.38 mg/kg was given as crystalline cocaine HCl. Oral cocaine was administered in doses of 2.0 and 3.0 mg/kg. Intranasal cocaine kinetics were described by a 1‐compartment open model with 2 consecutive first‐order input steps and first‐order elimination. Oral cocaine disposition was described by a 1‐compartment open… 
Kinetics of cocaine in humans after intravenous and intranasal administration.
There were statistically significant differences in the mean area under the concentration-time curve (AUC) following intravenous and intranasal administration and the AUC was dose-dependent and the fraction of the dose absorbed after 64 mg intran asal cocaine was significantly lower than after 96 mg dose.
Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.
Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile, and cocaine bioavailability values were similar to previous estimates.
Cocaine pharmacokinetics in humans.
Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers.
Cocaine accumulates in the body with chronic use resulting in a prolonged terminal elimination phase for cocaine and metabolites, which greatly exceeded previous estimates from studies of acute cocaine administration.
Cocaine pharmacodynamics after intravenous and oral administration in rats: relation to pharmacokinetics
Oral cocaine is more effective behaviorally than from predictions made in terms of its PK, and the differences in active metabolite profiles as well as the rate and extent of acute tolerance for IV versus PO cocaine may account for the greater potency observed for oral cocaine.
Determination of pharmacokinetics of cocaine in sheep by liquid chromatography.
The clearance of cocaine in sheep was much higher than cardiac output, and Pulmonary first-pass effect has been suggested as the possible explanation for the large clearance.
Kinetics of cocaine distribution, elimination, and chronotropic effects
The kinetic analysis demonstrated that the chronotropic effects of cocaine decline more rapidly than either plasma levels or biophase concentrations, and could be modeled as a first‐order process and is compatible with either the intervention of homeostatic reflex mechanisms or the phenomenon of acute tolerance.
Cocaine and metabolite concentrations in plasma during repeated oral administration: development of a human laboratory model of chronic cocaine use.
It is demonstrated that chronic oral dosing of cocaine produced dose-related increases in plasma cocaine concentration, and this model could be useful for studying the effects of chronic cocaine use in human subjects.
Pharmacokinetics of cocaine in maternal and fetal rhesus monkeys at mid-gestation.
It was found that intravenous administrations of cocaine produced maximal maternal levels of benzoylecgonine below the plasma levels for cocaine, whereas oral administrations resulted in the maximal maternal plasma levels of this metabolite significantly above those of cocaine.


Metabolism of cocaine in man
Ecgonine methyl ester, a product of cocaine hydrolysis by plasma cholinesterase, was identified as a major metabolite in the urine of both subjects and accounted for 32% to 49% of the urinary metabolites.
Acute systemic effects of cocaine in man: a controlled study by intranasal and intravenous routes.
The 100-milligram dose given intranasally and all of the doses given intravenously produced significant dose-related physiologic and subjective responses.
Oral cocaine: plasma concentrations and central effects.
Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally, and the subjective "highs" in man are greater after oral than after intranASal administration.
Kinetics of pharmacologic response to cocaine.
Cocaine plasma concentration-response-time data obtained from the literature were analyzed by pharmacokinetic methods and suggest that only about 20% of an oral dose of cocaine is absorbed intact into the systemic circulation.
Cocaine: Blood Concentration and Physiological Effect After Intranasal Application in Man
The excretion of cocaine metabolites after intranasal application of various doses in surgical patients and experimental subjects and the sensitivity of the EMIT method for detecting cocaine metabolites are reported.
Cocaine: plasma concentrations after intranasal application in man.
In that residual cocaine was detectable on the nasal mucosa for 3 hours, continuous absorption secondary to its vasoconstrictive action might explain its persistence in the plasma.
Cocaine plasma concentration: relation to physiological and subjective effects in humans.
Volunteer subjects with previous histories of cocaine use were administered cocaine hydrochloride intravenously or intranasally. There was a positive relationship between peak plasma concentration,
Cocaine and Succinylcholine Sensitivity: A New Caution
Cocaine was stable (93.6 ± 5.0 (SD) % remaining after 120 minutes) when incubated in plasma from six patients with histories of succinylcholine sensitivity and low dibucaine numbers (phenotype A),
Theoretical relationships between area under the curve and route of administration of drugs and their precursors for evaluating sites and pathways of metabolism.
The area under the blood concentration--time curve (AUC) for a drug and its metabolite is shown to be useful in determining the presence of these processes when a drug is administered concomitantly by different routes of administration.
Cocaine metabolism: Cocaine and norcocaine hydrolysis by liver and serum esterases
Benzoyl ecgonine, a major metabolite of cocaine formed by hydrolysis, was not produced enzymatically in either serum or liver; the rate of spontaneous formation at physiological pH suggests that this metabolite may arise nonenzymally in the body.