Metabolism withdrawal from

Petursson H, Lader MH Benzodiazepine dependence. BrJ Addict 76 133—143,1981a Petursson H, Lader MH Withdrawal from long-term benzodiazepine treatment. Br Med J (Clin Res Ed) 283 643—643, 1981b Pichard L, Gillet G, Bonfils C, et al Oxidative metabolism of zolpidem by human liver... 

Practolol (Figure 8.13) was the prototype cardioselective p-adrenoceptor blocking agent. Selectivity was achieved by substitution in the para position with an acetyl anilino function. The similarity of this drug with those outlined above is obvious. Practolol caused severe skin and eye lesions in some patients which led to its withdrawal from the market [6]. These lesions manifested as a rash, hyperkeratosis, scarring, even perforation of the cornea and development of a fibrovascular mass in the conjunctiva, and sclerosing peritonitis. Some evidence is available that the drug is oxidatively metabolized to a reactive product that binds irreversibly to tissue pro-... 

In a review of 37 reported cases, Davidson (426) found that the risk of seizures with bupropion was higher at doses above the recommended maximum (i.e., 450 mg per day). An increased risk of seizures was also noted in eating-disordered patients (i.e., bulimics) on bupropion, leading to its temporary withdrawal from the market. With the immediate release formulation, the seizure risk is four per 1,000 patients when the dose is kept at or below 450 mg per day in those without known risk factors (426, 468). The seizure risk may be as low as one per 1,000 patients with the sustained release formulation when the dose is kept below 450 mg per day and the patient has no preexisting seizure history and is not on any medication that also can lower seizure thresholds or interfere with the metabolism of bupropion. 

Absorption and metabolism The drug is absorbed rapidly from the small intestine (when empty of food). Levodopa has an extremely short half-life (1 to 2 hours), which causes fluctuations in plasma concentration. This may produce fluctuations in motor response ( on-off phenomenon), which may cause the patient to suddenly lose normal mobility and experience tremors, cramps, and immobility. Ingestion of meals, particularly if high in protein content, interferes with the transport of levodopa into the CNS. Large, neutral amino acids (for example, leucine and isoleucine) compete with levodopa for absorption from the gut and for transport across the blood-brain barrier. Thus levodopa should be taken on an empty stomach, typically 45 minutes before a meal. Withdrawal from the drug must be gradual. 

Caffeine has been associated with changes in the metabolism of clozapine (SEDA-20, 50 SEDA-22, 61). Seven schizophrenic patients taking clozapine monotherapy participated in a study of the effects of caffeine withdrawal from the diet (247). After a caffeine-free diet for 5 days, clozapine plasma concentrations fell by 50%. The authors suggested that schizophrenic patients treated with clozapine should have their caffeine intake medically supervised, and that monitoring of concentrations of clozapine and its metabolite may be warranted. 

Carrillo JA, Herraiz AG, Ramos SI, Benitez J. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients. J Clin Psychopharmacol 1998 18(4) 311-6. 

Brower KJ (1997) Withdrawal from anabolic steroids. Current Therapy in Endocrinology and Metabolism 6 338-343. 

However, opacities in lenses and dermatological side effects led to withdrawal from the market in 1962. Suspicion for development of the serious toxicides pointed to desmosterol, which, with no metabolic alternatives, simply accumulated. 

Ertapenem In two cases there was marked induction of valproate metabolism by ertapenem [349 ]. The first was a 47-year-old woman whose valproate concentrations rose after ertapenem withdrawal from <1 to 34 mg/1. The second was a 72-year-old woman with status epilepticus whose valproate concentrations continued to increase for several days after ertapenem withdrawal. 

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