Autoinduction

Cho, K. W., Colepicolo, P., and Hastings, J. W. (1989). Autoinduction and aldehyde chain-length effects on the bioluminescent emission from the yellow protein associated with luciferase in Vibrio fischeri strain Y-lb. Photochetn. Photobiol. 50 671-677. 

Half-life (t1/2) 18-27 hours (adult) greater than 36 hours (elderly or patients with renal impairment) Cytochrome P-450 (CYP450) isoenzyme t1/2 decreases over time due to autoinduction 25-65 hours (initial) 12-1 7 hours (adult multiple dosing) 8-14 hours (children multiple dosing) 2 hours (parent) 9 hours (metabolite) 5-20 hours (adult) 25 hours increases to 59 hours with concomitant valproic acid therapy... 

Zinc-containing compounds have also been used as catalyst. Recently, Trost et al. reported asymmetric aldol reactions of methyl ynones 331 with pyruvaldehyde ketals 330 in the presence of a dinuclear zinc catalyst 329 generated from ZnEt2 and a pentadentate 0,N,0,N,0-ligand (328, Scheme 168).428 This reaction is a unique case of enantioselective autoinduction with product incorporation into the catalyst and a reversal of the absolute configuration. 

Carbamazepine can induce its own metabolism (autoinduction) this effect begins within 3 to 5 days of dosing initiation and takes 21 to 28 days to become complete. 

During the first month of therapy, serum concentrations can decrease because of autoinduction of metabolizing enzymes, requiring a dose increase. 

Oxcarbazepine has mood-stabilizing effects similar to those of carbamaz-epine, but with milder side effects, no autoinduction of metabolizing enzymes, and potentially fewer drug interactions. There are fewer data supporting its efficacy than there are for carbamazepine s efficacy. 

Catalyst 329, prepared from trimethylaluminum and 3,3/-bis(triphenylsily 1)-1,1 /-bi-2-naphthol, allowed the preparation of the endo cycloadduct (2S )-327 with 67% ee. The use of non-polar solvents raised the ee, but lowered the chemical yield213. Recently, it was reported that the reaction to form 327 exhibited autoinduction when mediated by catalyst 326214. This was attributed to a co-operative interaction of the cycloadduct with the catalyst, generating a more selective catalytic species. A wide variety of carbonyl ligands were tested for their co-operative effect on enantioselectivity. Sterically crowded aldehydes such as pivaldehyde provided the best results. Surprisingly, 1,3-dicarbonyl compounds were even more effective than monocarbonyl compounds. The asymmetric induction increased from 82 to 92% ee when di(l-adamantyl)-2,2-dimethylmalonate was added while at the same time the reaction temperature was allowed to increase by 80 °C, from -80 °C to 0°C. 

Drug-drug interactions are often more problematic with carbamazepine than other mood stabilizers. Carbamazepine increases the activity of certain liver enzymes. Because these enzymes metabolize and eliminate medications and other substances introduced to the body, carbamazepine therapy can decrease the blood level and thereby reduce the effectiveness of itself (a phenomenon called autoinduction) and other medications that are metabolized by these enzymes. It is not unusual to find that the dose of carbamazepine must be increased after several weeks, because it has increased its own elimination. Other medications may likewise be less effective. Of particular concern are the oral contraceptives, Depo-Provera, and protease inhibitors used for the treatment of HI V+ patients. Oral contraceptives often require an increase in dose. 

In all these calculations, the basic assumption is the fixed relative composition of the catalytic species and the absence of modification of the catalyst by the products (autoinduction). On the contrary, the interpretation is more delicate and must take into account these perturbations. 

Tolerability" should not be confused with the term "tolerance", which describes the diminution in effects of a drug on prolonged exposure. Tolerance may be due to increased clearance because of autoinduction of the enzymes that metabolise the drug, such as occurs with some antiepileptic drugs, for example, carbamazepine. Tolerance may also result from altered pharmacodynamics, which is common with drugs acting on the CNS. 

Greatly increased clearance on repeat dosing because of autoinduction... 

Undergoes autoinduction. Half-life after repeated doses. 

Nevirapine has been shown to be an inducer of hepatic cytochrome P450 metabolic enzymes 3A4 and 2B6. The pharmacokinetics of autoinduction are characterized by an approximately 1.5- to 2-fold increase in the apparent oral clearance of nevirapine as treatment continues from a single dose to 2 to 4 weeks of dosing with 200 to 400 mg/day. Auto-induction also results in a corresponding decrease in the terminal phase half-life of nevirapine in plasma from approximately 45 hours (single dose) to approximately 25 to 30 hours following multiple dosing with 200 to 400 mg/day. 

Autoinduction protocoi with the methionine auxotroph B834... 

The supernatant is removed and the pellet resuspended in 2 ml PBS before inoculation into 1L of autoinduction SeMet media (1 L SeMet Base, 20 ml OnEx Solution 1,50 ml OnEx Solution 2,1 ml OnEx Solution 3,50 ml SeMet glucose-free nutrient mix and 4 ml 10 mg/ml selenomethionine) which contains antibiotics. 

IPTG induction protocol using the poisoning Autoinduction protocol using the poisoning ... 

This method follows the same protocol as for production of The method follows that for autoinduction using the... 

Most of the drug interactions with carbamazepine are related to its effects on microsomal drug metabolism. Carbamazepine can induce its own metabolism (autoinduction) after prolonged administration, decreasing its clearance rate, half-life, and serum concentrations. The possibility of autoinduction requires the clinician to reevaluate the patient s blood levels after a month of carbamazepine therapy. The autoinduction phenomenon is over in about a month. 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

Geriatric Considerations - Summary Well-tolerated in older adults. Adjust dose based on creatinine clearance. Autoinduction of metabolism does not occur as seen with carbamazepine, but drug interactions are still an issue. Many of the CNS effects occur early in treatment and are transitory. One-third of patients with hypersensitivity reactions to carbamazepine will experience cross-sensitivity to oxcarbazepine. 

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