Pharmacokinetic Determinants of Drug Abuse and Dependence

  title={Pharmacokinetic Determinants of Drug Abuse and Dependence},
  author={Usoa E. Busto and Edward Sellers},
  journal={Clinical Pharmacokinetics},
SummaryDrugs that produce physical dependence or have similar pharmacological profiles to highly abused drugs are unlikely to be considered acceptable for marketing. Thus, the prediction of abuse and dependence becomes an important issue in the development of new psychotropic drugs.Both pharmacokinetic and non-pharmacokinetic factors play an important role in predicting dependence and abuse liability of drugs. Evidence for the importance of pharmacological factors includes: (a) the… 

Pharmacokinetic considerations in abuse liability evaluation.

Variations in drug metabolism may be related to dose-dependent kinetics, first-pass metabolism, and variations in genetic traits (e.g. poor or extensive metabolizers).

Clinical Pharmacokinetics of Non-Opiate Abused Drugs

The clinical significance of kinetic characteristics with respect to abuse is discussed where possible and the pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance.

Pharmacologic aspects of benzodiazepine tolerance and dependence.

Pharmacokinetic and Pharmacodynamic Principles of Illicit Drug Use and Treatment of Illicit Drug Users

It is important to consider pharmacotherapy as only one potential part of the treatment of illicit drug users, as with all patients consuming multiple drugs, illicit drugusers are prone to developing drug interactions.

The role of pharmacogenetically-variable cytochrome P450 enzymes in drug abuse and dependence.

It is anticipated that pharmacogenetics will be used to identify individuals at a greater risk for specific drug dependencies, provide information that can lead to novel treatment and prevention approaches as well as provide guidance for individualization of treatment choice.

Pharmacokinetic Changes in the Elderly

The available data are not sufficient for a definitive conclusion on whether the pharmacokinetic changes in the elderly translate to an increase in the abuse and dependence potential of alcohol, benzodiazepines or opioids.

Abuse liability assessment for biologic drugs – All molecules are not created equal




Drug Kinetics and Alcohol Ingestion

Systematic studies of the mechanism of alcohol kinetic interactions are needed and such kinetic studies should be combined with pharmacodynamic measures in order to establish the clinical importance of changes in drug kinetics.

Benzodiazepines: a summary of pharmacokinetic properties.

Drugs in this category have long-acting pharmacologically active metabolites, accumulate extensively during multiple dosage, and may have impaired clearance in the elderly and those with liver disease.

The Relationship of Pharmacokinetics to Pharmacological Activity: Morphine, Methadone and Naloxone

Based on urinary excretion data in man, accelerated morphine metabolism and excretion do not contribute to morphine tolerance and the rapid onset of the narcotic antagonist action of naloxone can be related to its rapid entry into the brain, whereas its potency stems in part from its high lipid solubility which allows a high brain concentration.

Physical dependence to barbital compared to pentobarbital. IV. Influence of elimination kinetics.

  • N. BoisseM. Okamoto
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1978
These findings conclusively support the key role of the rate of barbiturate elimination to expose underlying physical dependence to barbiturates.

Diazepam tapering in detoxification for high‐dose benzodiazepine abuse

Gradual reduction of diazepam dose appears to be an effective and safe approach for detoxifying abusers of high doses of benzodiazepines.

Pharmacokinetic properties of benzodiazepine hypnotics.

The kinetic properties of three benzodiazepine hypnotics are reviewed. Flurazepam serves as a precursor for at least two rapidly appearing and rapidly cleared metabolites that may contribute to sleep

Assessment of the Abuse Potentiality of Morphinelike Drugs (Methods Used in Man)

In an attempt to develop analgesics, antitussives, and antidiarrheals that were devoid of those properties of morphine leading to abuse, a large number of drugs have been synthesized and studied.

Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: A kinetic approach

Slow infusion of large amounts of phenobarbital provides a safe, efficacious single‐dose treatment in patients with clinical hypnosedative withdrawal reactions until patients slept but were arousable.

Dependence liability of several sedative-hypnotic agents evaluated in monkeys.

Dependence liability of 10 drugs was tested in rhesus monkeys and benzoctamine and perlapine were found to be dependence-free drugs.

Clinical Pharmacokinetics of the Newer Benzodiazepines

The most unique of the newer benzodiazepine derivatives are the ultra-short half-life (oxidised) compounds midazolam, triazol am and brotizol am, which are essentially non-accumulating during multiple dosage.