ABSTRACT
Aim: The overdose of caffeine, a cytochrome P450 1A2 probe, in young women has become a problem. The aim of this study was to evaluate possible drug interactions between intentionally overdosed caffeine (12 g) and oral contraceptive doses of ethinyl estradiol prescribed to a young woman in a suicide attempt. Methods: The serum concentrations of caffeine in the patient and the time-dependent ethinyl estradiol inhibition of caffeine oxidation in vitro were evaluated. Results: The serum concentration of caffeine 4 h after overdose was 136 µg/mL; from the data obtained between 4 and 28 h after overdose, the half-life was estimated to be 33 h, which is many times larger than the normal value. Prescribed ethinyl estradiol prolonged caffeine elimination in vivo and inhibited paraxanthine formation, as evidenced by the low serum concentrations. In human liver microsomes, ethinyl estradiol (50 nM) inhibited half of caffeine N 3 -demethylation. Pre-incubation of human liver microsomes with ethinyl estradiol resulted in a powerful time-dependent inhibitory effect on caffeine N 3 -demethylation in human liver microsomes. Conclusion: These results suggest that a prescription history of contraceptives at clinical doses may have a strong effect on the pharmacokinetics of overdosed caffeine in young women, resulting in dangerous drug interactions.
ABSTRACT
Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.