Evaluation of the Influence of Diabetes Mellitus on Antipyrine Metabolism and CYP1A2 and CYP2D6 Activity

Abstract

The metabolism of antipyrine is increased in patients with type 1 diabetes. Based on in vitro reports of antipyrine metabolism and current caffeine metabolic index data, the predominant effect of type 1 diabetes appears to be an increase in CYP1A2 activity. Assessment of the effect of the disease on other specific CYP metabolic pathways is warranted.

Decreased exposure of simvastatin and simvastatin acid in a rat model of type 2 diabetes

“…Accumulating reports have shown that diabetes alters the metabolism rates of drugs via affecting activities and expressions of CYP450s and drug transporter in the liver [15,17,20,35] . Simvastatin, a substrate of Cyp3 and Oatp2/OATP1B1, is often used for improving hypercholesterolemia associated with DM.…”

Cytochrome P450 mediated-drug metabolism is reduced in children with sepsis-induced multiple organ failure

“…Blood samples (1 ml) were obtained at 0, 6, 12, 24, and 48 h. The samples were collected in sodium citrate containing tubes, centrifuged immediately, and the plasma was frozen at −70°C and stored for batch analysis. Antipyrine plasma concentrations were determined using HPLC as previously described [14]. The elimination rate constant (k), elimination half-life (t 1/2 =0.693/k), and apparent oral clearance (CL/F=k e ×Vd) of antipyrine were calculated using standard methods.…”

Effective Dosing Regimen of 1-Aminobenzotriazole for Inhibition of Antipyrine Clearance in Guinea Pigs and Mice Using Serial Sampling

“…The projected P450 inactivations at the plasma C max of ABT agreed with the inhibitions of P450-mediated AP clearance observed in vivo. For mechanistic studies in vivo overall, a 2-h prior oral pretreatment with ABT at 50 mg/kg in mice and 100 mg/kg in guinea pigs would provide significant systemic concentrations of the inhibitor over 24 h and inhibition of P450-dependent clearance of test compounds.In our last communication (Balani et al, 2002), the dosing regimen of 1-aminobenzotriazole (ABT), a nonspecific inhibitor of cytochromes P450 (P450s) (Huijzer et al, 1989;Constan et al, 1999), was established in rats, dogs, and monkeys to effectively inhibit P450s and hence decrease the plasma clearance and increase the exposure of antipyrine (AP), a nonspecific probe substrate of P450s (Engel et al, 1996;Sharer and Wrighton, 1996;Matzke et al, 2000). All P450s were shown to be affected by ABT treatment (Balani et al, 2002).…”

“…In our last communication (Balani et al, 2002), the dosing regimen of 1-aminobenzotriazole (ABT), a nonspecific inhibitor of cytochromes P450 (P450s) (Huijzer et al, 1989;Constan et al, 1999), was established in rats, dogs, and monkeys to effectively inhibit P450s and hence decrease the plasma clearance and increase the exposure of antipyrine (AP), a nonspecific probe substrate of P450s (Engel et al, 1996;Sharer and Wrighton, 1996;Matzke et al, 2000). All P450s were shown to be affected by ABT treatment (Balani et al, 2002).…”