CPT-11 belongs to the class of topoisomeraseⅠ inhibitors and is a prodrug of SN-38. It is extensively metabolized in the liver and is partially excreted by the kidney. Therefore, for patients with renal insufficiency, CPT-11 dose modification is not required. In addition, the relationship between renal function and CPT-11 adverse events has not been explored. However, a recent study showed that the elimination of SN-38 was significantly delayed in patients with severe renal failure compared to that in patients with normal renal function. To demonstrate the relationship between adverse events (hematotoxicity) of CPT-11 and renal function, we retrospectively investigated 40 lung cancer patients who first received combination therapy of irinotecan and carboplatin at the Hokkaido Keiaikai Sapporo Minami-sanjo Hospital. The subjects of the survey had nadir levels of renal function and blood count from the first cycle to the next. Correlation was observed between: 1) Renal function parameters and white blood cell count, 2) renal function parameters and neutrophil count, 3) renal function parameters and hemoglobin level. Furthermore, significant negative correlations were observed between renal function parameters and age. These correlations indicate that hematologic toxicities were not directly related to renal function, but were dependent on age, and suggest that age-related functional decline of the organ might have influence on hematologic toxicities.
Given its widespread incidence, there are many opportunities for healthcare professionals to have contact with chronic kidney disease (CKD) patients. In addition, dose adjustment is necessary when a renally-excreted drug is administered to CKD patients, and an accurate understanding of renal function is therefore necessary for appropriate dispensing as drug clearance will depend on renal function. Creatinine clearance (CCr) is a well-established measure of renal function over time, although the estimated quantity of Malpighian tuft filtration [estimated glomerular filtration rate (eGFR)] can be used to evaluate current renal function. For GFR estimation other than that proposed by the Japanese Society of Nephrology, results can be easily calculated, and even clinical practice is frequently used. However, many health-care institutions continue to use CCr as standard. Therefore, we evaluated the degree of understanding of renal function evaluation among pharmacists in Ehime to benefit the nephrology and pharmacotherapy study group in Ehime by raising the renal function evaluation skill level in the entire region. A questionnaire survey was distributed to all pharmacists at 129 hospitals that were registered with the hospital pharmacist society of Ehime and 558 community pharmacists registered with the Ehime pharmacist society.Specifically related to eGFR measurements, the understanding was that ml/min/1.73m2 and ml/min was a low value and, particularly for understanding of eGFR, the possibility of over-estimation of renal function was suggested. Given that Ehime pharmacists displayed a limited understanding of renal function evaluation, and to ensure safer medication use in the future, it is clear that further clarifying research by the study group of nephrology and pharmacotherapy in Ehime is necessary.
Aluminum hydroxide and magnesium hydroxide have been reported to attenuate the action of rosuvastatin, an HMG-CoA reductase inhibitor, but the mechanism is not fully understood. Lanthanum carbonate contains the polyvalent metal lanthanum, which may interact similarly with HMG-CoA reductase inhibitors. Therefore, we surveyed 29 patients being treated chronically with rosuvastatin who began treatment with lanthanum carbonate. The study consisted of 29 patients, further investigated six patients in the rosuvastatin group and 23 patients in the non-rosuvastatin group. Low-density lipoprotein (LDL) cholesterol levels in all subjects before and after the start of treatment with lanthanum carbonate were 73.0±19.8 mg/dL and 72.8±22.6 mg/dL, respectively (p = 0.498). LDL cholesterol levels have observed no changes during the investigation period. This has been similar in the rosuvastatin and non-rosuvastatin groups. Serum phosphorus levels in all subjects before and after the start of lanthanum carbonate treatment were 6.6±0.9 mg/dL and 5.4±1.2 mg/dL, respectively (p＜0.01). In the rosuvastatin group, the corresponding levels were 6.2±0.8 mg/dL and 5.0±1.0 mg/dL before and after the start of treatment with lanthanum. In the non-rosuvastatin group, the corresponding levels were 6.7±0.9 mg/dL and 5.5±1.2 mg/dL before and after the start of treatment with lanthanum, with a significant reduction in the levels being observed during the investigation period (p<0.01). LDL cholesterol levels were almost unchanged in all subjects examined, and the serum phosphorus levels decreased in all subjects examined. Therefore, our results suggest that the combined use of lanthanum carbonate and rosuvastatin does not affect the clinical effect of either medication.
The supplemental pregabalin (PGN) doses after hemodialysis (HD) were described on the basis of simulation data of administration at 6 hours prior to starting HD on drug PGN package inserts. However, it is unclear whether supplemental PGN is necessary after HD. Therefore, we investigated the pharmacokinetics of PGN by measuring the plasma concentration in two HD patients. The PGN doses were 50 mg/day. Plasma PGN concentrations were measured at seven points from the day of HD to the next non-HD day.The true removal rates during HD were 55.6% and 37.8%, the dialysis PGN clearance was 109.5mL/min and 74.6mL/min, and the half-life of PGN was 35 hours and 89 hours on non-HD day for the two cases, respectively. The contribution ratio of HD in PGN removal were only 9.6%, and 4.9%, as compared with normal renal function. The ratios of the estimated AUC on the HD day (eAUCHD) versus that on the non-HD day (eAUCnonHD) were 85.3% and 85.7% for the two cases, respectively.The half-life of PGN on non-HD day was markedly extended compared to that in healthy subjects; eAUCHD against eAUCnonHD differed by only 15%, and the contribution ratio of HD in PGN removal was low.Our data indicate that supplemental PGN administration might not be necessary following HD if PGN dosage for a creatinine clearance < 15mL/min is administered after HD closure.