Pharmacokinetics in morbid obesity: influence of two bariatric surgery techniques on paracetamol and caffeine metabolism

The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function). In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study. Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery. Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).Peer ReviewedPostprint (author's final draft

Psychostimulant drugs for cocaine dependence.

Objective: To ascertain the efficacy of psychostimulants for cocaine dependence on cocaine use, sustained cocaine abstinence and retention in treatment. The influence of type of drug, comorbid disorders and clinical trial reporting quality over psychostimulants efficacy has also been studied. Cocaine dependence is a frequent disorder for which no medication has clearly proved to be efficacious. Substitution therapy involves the replacement of abused drug, which is often illegal, used several times a day, by a legal, orally administered one. A substitutive drug has similar effects to the abused one, but with a lower addictive potential therefore leading to drug abstinence and involving patients to follow medical and psychological assistance. This strategy has proved to be efficacious for heroin and nicotine dependence. In this review we investigated if psychostimulant substitution was efficacious for cocaine dependence. We found that sixteen studies that had enrolled 1,345 patients investigated the efficacy of psychostimulants against placebo for cocaine dependence. Seven drugs with psychostimulant effect or metabolized to a psychostimulant have been investigated: bupropion, dexamphetamine, methylphenidate, modafinil, mazindol, methamphetamine and selegiline. Psychotherapy was provided in all clinical trials. Study length ranged from 6 to 24 weeks. Psychostimulants did not improve cocaine use, had an unclear beneficial effect over sustained cocaine abstinence and were not associated with higher retention in treatment. Psychostimulants did not increase risk of serious adverse events. It was found that psychostimulants could be efficacious for some groups of patients, such as methadone maintained dual heroin-cocaine addicts. Therefore, psychostimulants, though have not proved yet their efficacy for cocaine dependence, deserve further investigation

Efficacy of psychostimulant drugs for amphetamine abuse or dependence.

Amphetamine dependence constitutes a public health problem with many consequences and complications. Amphetamine abuse refers to a maladaptive and hazardous pattern of use considered to be less severe than dependence. To date, no pharmacological treatment has been approved for amphetamine abuse or dependence, and psychotherapy remains the best treatment option. Long-term amphetamine use reduces dopamine levels in the brain. Drugs increasing dopamine and mimicking the effects of amphetamines with lower abuse liability could be used as replacement therapy in amphetamine dependence. Several psychostimulants have been studied recently for this purpose. In this review, the efficacy and safety of psychostimulants for amphetamine abuse or dependence were studied. We found eleven studies enrolling 791 amphetamine-dependent participants and assessing the effects of four different psychostimulants: dexamphetamine, bupropion, methylphenidate and modafinil. Psychosocial interventions were additionally provided to all participants. The studies were conducted in the USA, Australia or Northern Europe, and study length ranged from 8 to 20 weeks. Psychostimulants did not reduce amphetamine use or amphetamine craving and also did not increase sustained abstinence in comparison with placebo. Retention in treatment was similar and low with both treatments. Psychostimulants also did not increase the risk of adverse events that were intense enough to induce dropouts. Research with larger and longer trials is needed to determine whether psychostimulants can be a useful replacement therapy for patients with amphetamine abuse or dependence. The design of future trials should consider the level of dependence at study entry, the potency and the dose of the psychostimulant administered, the length of the trial and the representativeness of included participants

Pharmacokinetics in morbid obesity: influence of two bariatric surgery techniques on paracetamol and caffeine metabolism

The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function). In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study. Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery. Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).Peer Reviewe