Acute poisoning by pirimicarb: clinical and toxicological features.

Objective: Anticholinesterase compounds like organophosphorous and carbamates account for the majority of poisonings by the insecticides class agents. While the toxicokinetic depends on the extent of exposure and also on the chemical structure of the agent, the clinical symptoms range from the classic cholinergic syndrome to flaccid paralysis and intractable seizures. The carbamate ester pirimicarb (Pirimor), a toxic N-dimethylcarbamate pesticide, is used as insecticide.

Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms.

Aims: To evaluate whether simvastatin influences (i) the intestinal expression of P-glycoprotein (P-gp) and MRP2, and (ii) the disposition of the beta(1)-selective blocker talinolol, a substrate of these transporter proteins.

Methods: The disposition of talinolol after intravenous (30 mg) and single or repeated oral administration (100 mg daily) was monitored before and after chronic treatment with simvastatin (40 mg daily) in 18 healthy subjects (10 males, eight females, body mass index 19.0-27.

Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans.

Background And Methods: The antiepileptic drug carbamazepine is known to be an inducer of cytochrome P450 (CYP) 3A4 after binding to the nuclear pregnane X receptor. To evaluate whether it also regulates the multidrug transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein MRP2 in humans, duodenal expression of multidrug resistance gene MDR1 messenger ribonucleic acid (mRNA) and MRP2 mRNA, content of P-gp and MRP2, and disposition of the nonmetabolized P-gp substrate talinolol after intravenous (30 mg) and long-term oral administration (100 mg for 19 days) were assessed in 7 healthy subjects (age, 23-35 years; body weight, 64-93 kg) before and after comedication of carbamazepine (600 mg for 14-18 days).

Results: Carbamazepine medication was associated with increased urinary excretion of D-glucaric acid and induction of carbamazepine elimination.

CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects.

Background: Clinical trials have indicated that the combined beta- and alpha-adrenergic receptor blocker carvedilol improves the survival rate in patients with advanced chronic heart failure. The objective of our study was the identification and quantification of factors that modulate steady-state serum concentrations of carvedilol and its enantiomers and that may influence therapeutic efficacy and safety.

Methods: The influence of genetic variants of cytochrome P450 (CYP) 2D6 and CYP2C9 and of transporter proteins (P-glycoprotein, multidrug resistance protein 2 [MRP2]) on the disposition of carvedilol and its enantiomers after intravenous (5 mg) and long-term oral administration (25 mg for 7 days) was assessed in 12 healthy subjects.

Effect of levothyroxine administration on intestinal P-glycoprotein expression: consequences for drug disposition.

Objective: Thyroid function alters the pharmacokinetics of many drugs; one example is the cardiac glycoside digoxin. Because digoxin disposition is affected by intestinal expression of P-glycoprotein, we hypothesized that thyroid hormones may regulate P-glycoprotein and influence disposition of P-glycoprotein substrates.

Methods: Duodenal expression of P-glycoprotein measured by reverse transcriptase-polymerase chain reaction of MDR1 messenger ribonucleic acid (mRNA) and by immunohistochemical examination was studied in 8 healthy volunteers (4 men and 4 women; age range, 22-29 years; body weight, 59-89 kg) before and after coadministration with levothyroxine (200 microg orally for 17 days), which resulted in suppression of thyroid-stimulating hormone.

Association of time to recurrence with thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression in stage II and III colorectal cancer.

Patients with International Union Against Cancer (UICC) stage IIb and III colon cancer and stage II and III rectal cancer may receive adjuvant chemotherapy with 5-fluorouracil (5-FU). High levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have been associated with resistance to 5-FU in advanced colorectal cancer. The aim of this study was to investigate the association of TS and DPD mRNA levels with recurrence-free survival in patients with colorectal cancer who are receiving adjuvant 5-FU-based chemotherapy.