Effects of 5-fluorouracil Co-administration on Blood Pressure in Patients Maintained on Antihypertensives: a Retrospective Case Series.

This study aimed to investigate the possible drug-drug interactions (DDIs) of 5-FU with antihypertensives metabolised by CYP3A4 and 2C9, using blood pressure (BP) as a pharmacodynamic (PD) parameter. Patients who received 5-FU in combination with antihypertensives metabolised by CYP3A4 or 2C9, specifically, a) amlodipine, nifedipine, or amlodipine + nifedipine, b) candesartan or valsartan, or c) amlodipine + candesartan, amlodipine + losartan, or nifedipine + valsartan, (Group A, n = 20) were identified. Patients who received 5-FU with WF and antihypertensives, specifically, a) amlodipine or b) amlodipine + telmisartan, amlodipine + candesartan, or amlodipine + valsartan, (Group B, n = 5) or 5-FU alone (Group C, n = 25) were also identified and analysed as a comparator and control group, respectively. Regarding the peak BP levels during chemotherapy, there was a significant increase in both SBP (P < 0.0002 and 0.0013) and DBP (P = 0.0243 and 0.0032) in Groups A and C, respectively (Tukey-Kramer test). In contrast, although SBP also increased in Group B during chemotherapy, the change was not statistically significant and there was a decrease in DBP. The significant increase in SBP can be attributed to chemotherapy-induced hypertension by 5-FU or other drugs in the chemotherapeutic regimens. However, when comparing the lowest BP levels during chemotherapy, there was a decrease in SBP and DBP in all groups from the baseline values. The median time to peak and lowest BP was at least 2 weeks and 3 weeks, respectively, for all groups, suggesting that a BP lowering effect was observed following the offset of the initial chemotherapy-induced hypertension. At least 1 month after 5-FU chemotherapy, the SBP and DBP returned to baseline values in all groups. Since Group B also showed a significant increase in PT-INR, possibly demonstrating 5-FU inhibition of CYP activity and, consequently, of WF metabolism, it is likely that 5-FU also inhibited the metabolism of the antihypertensive drugs. The findings suggest possible DDIs between 5-FU and antihypertensives metabolised by CYP3A4.

Measurement of zinc concentration in blood and breast milk of a Wilson's disease patient taking zinc acetate.

Case: A 27-year-old, gravida 2, para 0, Japanese female who was maintained on zinc acetate (75 mg/day) during pregnancy expressed her desire to breastfeed after birth. We investigated the possibility of breastfeeding while on treatment. Breast milk zinc concentrations were determined using an atomic absorption photometer. Breast milk zinc concentrations on the 4th (colostrum) and 32nd (post-colostrum) days post partum were 10.80 µg/mL and 3.28 µg/mL, respectively. These values are less than the reported range of breast milk zinc concentrations in Japanese women who are not under any medication. Conclusion: We measured blood and breast milk zinc concentrations of a patient with Wilson's disease who was taking zinc acetate (75 mg/day). Zinc values were within the range of breast milk concentrations of mothers who are not on zinc acetate.

Applicability of hemodialysis clearance parameter for vancomycin therapeutic drug monitoring during continuous hemodiafiltration in an infant.

Cases requiring vancomycin administration planning in infants undergoing continuous hemodiafiltration (CHDF) are extremely rare. Here, we report a single case in which vancomycin therapeutic drug monitoring and administration planning were implemented for an infant requiring CHDF. The patient was diagnosed with wound infection after gastrostomy and enterotomy surgery and received vancomycin treatment for infection with methicillin-resistant Staphylococcus epidermidis. The vancomycin trough serum concentration was successfully controlled within the acceptable range. Additionally, we discuss the potential usefulness of applying the CHDF clearance parameter for the fine management of vancomycin serum concentration in a pediatric patient undergoing CHDF.

Implications of Clinical Mycophenolate Mofetil Dose According to Individual Body Weight in Japanese Renal Transplant Recipients.

BACKGROUND: Mycophenolate mofetil (MMF) is generally administered at a fixed dose of 0.5-1.5 g/d without considering individual body weight (BW) in Japanese renal transplant outpatients receiving maintenance therapy. We aimed to investigate the implications of the area under the curve of mycophenolic acid (MPA AUC):MMF dose ratio by individual BW and suggest the index of MMF dose according to individual BW. METHODS: Forty-three Japanese patients who received a renal transplant ≥6 months before the study were enrolled. Blood samples were collected at 4 time points: at predose, 20 minutes, 1 hour, and 3 hours after MMF administration. RESULTS: The mean ± standard deviation MMF dose, MPA AUC, and BW of all patients were 581 ± 207 mg/d, 36.2 ± 18.7 µg·h/mL, and 56.3 ± 11.1 kg, respectively. Patients with a lower BW tended to have a higher MPA AUC:MMF dose ratio than patients with a higher BW. There was a significant correlation between the MMF dose:BW ratios and MPA AUC (r(2) = 0.330; P < .01). The rate of MPA AUC between 30 and 60 µg·h/mL with the MMF dose:BW ratio of 10-16 mg/kg was 73.7%. CONCLUSION: Individual BW seems to affect the MPA AUC:MMF dose ratio; therefore, we need to consider individual BW when deciding on a MMF dose. The MMF dose:BW ratio of 10-16 mg/kg could predict MPA AUC between 30 and 60 µg·h/mL with a probability of approximately 75%. Therefore, it could be a useful index for outpatients, because it is difficult to draw blood frequently from such patients.