Differences In Nephrotoxicity Research Articles

Cisplatin, rather than oxaliplatin, increases paracellular permeability of LLC-PK1 cells via activating protein kinase C

The clinical use of cisplatin is limited by its adverse events, particularly serious nephrotoxicity. It was clarified that cisplatin is transported by a kidney-specific organic cation transporter (OCT2). OCT2 also mediates the uptake of oxaliplatin into renal proximal tubular cells; however, this agent does not lead nephrotoxicity. In the present study, we carried out comparative experiments with cisplatin and oxaliplatin using porcine kidney LLC-PK1 cell monolayers. In the fluorescein-labeled isothiocyanate-dextran flux assay, the basolateral application of cisplatin, but not oxaliplatin, resulted in an increase in the paracellular permeability of cell monolayers. Even though the cellular accumulation of platinum at 50 μM oxaliplatin could reach the same level at 30 μM cisplatin, oxaliplatin did not induce hyper-permeability in cell monolayers. Cisplatin, but not oxaliplatin, significantly activated PKC. In addition, the combination of PKC inhibitors recovered the increase in paracellular permeability. In conclusion, pharmacodynamic mechanisms via PKC could explain the difference in nephrotoxicity between cisplatin and oxaliplatin.

Differences in Nephrotoxicity between Modes of Iodinated Contrast Material Administration in Patients Suspected of Having Coronary Artery Disease.

Differences in Nephrotoxicity between Modes of Iodinated Contrast Material Administration in Patients Suspected of Having Coronary Artery Disease.

Colistin Nephrotoxicity in Adults: Single Centre Large Series from India.

Context:Limited Indian data are available on the rate of colistin nephrotoxicity and other risk factors contributing to the development of this important side effect.Aim:This study aims to generate data on colistin nephrotoxicity from a large cohort of Indian patients.Design:Retrospective cohort study.Materials and Methods:Case record analysis of patients who received colistin, in an oncology center in India, between January 2011 and December 2015. Nephrotoxicity was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria.Statistical Analysis:P < 0.05 was considered as statistically significant.Results:Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE. Abnormal RIFLE group (n = 30), in comparison to the normal renal function group (n = 199), had higher number of patients in intensive care unit (ICU) (96% vs. 79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II) score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P = 0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001). Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039). There was no significant difference in nephrotoxicity between 6 and 9 MU/day dosing pattern (8.8% vs. 13.8%, P = 0.058).Conclusion:Nephrotoxicity rate in our retrospective single center large series of patients receiving colistin was 13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease severity are at higher risk of nephrotoxicity while on colistin. A daily dose of 9 million does not significantly increase nephrotoxicity compared to the 6 million. Concomitant administration of vancomycin with colistin increases the risk of nephrotoxicity.

Randomized Controlled Trial to Determine the Efficacy of Early Switch From Vancomycin to Vancomycin Alternatives as a Strategy to Prevent Nephrotoxicity in Patients With Multiple Risk Factors for Adverse Renal Outcomes (STOP-NT).

Use of alternative antimicrobials to vancomycin is a potential strategy to reduce acute kidney injury (AKI) in high-risk patients, but current data do not support widespread adoption of this practice. To determine the efficacy of early switch to a nonnephrotoxic alternative for prevention of AKI in high-risk patients who receive vancomycin. This was an IRB-approved, prospective randomized controlled trial in a single, tertiary care academic medical center. Patients initially prescribed vancomycin between October 2011 to April 2013 with at least 2 risk factors for AKI were included. Treatment randomization was stratified by indication for therapy. Patients were randomized to continuation of dose-optimized vancomycin or early switch to an alternative antimicrobial agent. The primary end point was nephrotoxicity by consensus guideline definition adjudicated by blinded review; the secondary end point was AKI network-defined AKI. A total of 103 patients were randomized; 100 were included in the modified intent-to-treat population, 51 in the vancomycin group and 49 in the alternative group. The incidence of nephrotoxicity was 6.1% in the alternative therapy arm and 9.8% in the vancomycin group ( P = 0.72). The incidence of AKI was 32.7% in the alternative therapy group and 31.4% in the vancomycin group ( P = 0.89). No significant difference in nephrotoxicity or AKI was detected among patients treated with alternative antimicrobials compared with vancomycin. The use of alternative antimicrobial therapy instead of vancomycin solely for the purpose of preventing AKI in high-risk patients does not appear to be warranted.

Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience.

BackgroundVancomycin (VCM) requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP) on attaining target VCM trough concentrations and pharmacokinetics (PK)/pharmacodynamics (PD) parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.Materials and methodsThe ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation) and from April 2012 to December 2014 (postimplementation), 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51). In 65 patients (pre, n=15; post, n=50), 24-hour area under the concentration–time curve (AUC 0–24 h)/minimum inhibitory concentration (MIC) ratios were calculated.ResultsPharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33). The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL) was significantly higher during postimplementation (84%, 43/51) than during preimplementation (39%, 11/28) (P<0.01). The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400) was significantly higher during postimplementation (84%, 42/50) than during preimplementation (53%, 8/15; P=0.013). There were no significant differences in nephrotoxicity or mortality rate.ConclusionOur ASP increased the percentage of patients that attained optimal VCM trough concentrations and PK/PD parameters, which contributed to the appropriate use of VCM in patients with MRSA infections.

Species differences in methotrexate-induced hepatotoxicity and nephrotoxicity: Rabbits resist methotrexate nephrotoxicity

Background: Animal models are important tools for studying drug-induced toxicity. Species differences in drug-induced nephrotoxicity or hepatotoxicity was frequently reported, however, clear evidence of species differences in nephrotoxicity or hepatotoxicity induced by methotrexate (MTX) is not available. Aim: The present study was designed to investigate nephrotoxicity or hepatotoxicity of MTX in mice and rabbits. Methodology: twelve rabbits and 16 mice were used for the study. Each species of animals was divided into 2 groups; control and MTX treatedgroups. The control groups were treated with normal saline intra-peritoneum (IP), MTX was given IP in a dose of 20 mg/kg/weekly for 38 days for the rabbits and at a dose of 10mg/kg/ weekly for 23 days for mice. Serum levels of liver enzymes, urea, creatinine, Malondialdehyde (MDA) and MDA in liver homogenate were estimated for the rabbits. In mice, glutathione (GSH) and MDA were estimated in liver and kidney homogenates. Histopathological examination of the kidney and liver was done for the 2 species. Results: In the rabbits, MTX resulted in a significant increase in liver enzymes, and in MDA levels of serum, liver and kidney homogenates, while the levels of urea and creatinine were not affected. Histopathological changes suggestive of liver damage were seen, while the kidneys appeared normal on histopathological examination. In the mice, MTX resulted in a significant increase in MDA in the liver homogenates with a small and insignificant reduction in GSH. In mice kidney homogenates, MTX had not affected MDA, while GSH was significantly reduced. Histopathological examination in mice showed significant damage in both liver and kidney. Conclusion: MTX produced hepatotoxicity in rabbits and mice but nephrotoxicity occurred in mice only. This suggests that rabbits might be resistant to MTX induced nephrotoxicity

Is colistin effective in the treatment of infections caused by multidrug-resistant (MDR) or extremely drug-resistant (XDR) gram-negative microorganisms in children?

The increasing incidence of infections caused by multidrug-resistant (MDR) or extremely drug-resistant (XDR) gram-negative organisms has led to the reemergence of colistin use. Clinical and demographic data were collected on 94 pediatric patients diagnosed with MDR or XDR gram-negative infections and treated with either a colistin-containing regimen (colistin group) or at least one antimicrobial agent other than colistin (noncolistin group). The overall clinical response rates were 65.8% in the colistin group and 70.0% in the noncolistin group (P = 0.33). The infection-related mortality rates were 11% in the colistin group and 13.3% in the noncolistin group (P = 0.74). There was no statistically significant difference in nephrotoxicity in the colistin and noncolistin groups. Colistin therapy was at least as effective and as safe as beta-lactam antibiotics or quinolones, with or without aminoglycosides, in the treatment of infections caused by gram-negative organisms and may be a therapeutic option in children.

Physicochemical properties of radiographic contrast media, potential nephrotoxicity and prophylaxis.

Contrast induced nephropathy (CIN) remains a controversial topic. The clinical relevance of changes in laboratory parameters has been challenged; some authors have even suggested that CIN simply reflects natural fluctuations. Other areas of controversy include the pathophysiology of CIN, effectiveness of prophylactic approaches and differences in nephrotoxicity between individual contrast media (CM). The aim of this review is to summarize the current understanding of laboratory findings and explore its relationship to CM toxicity.

Top Guns: The "Maverick" and "Goose" of Empiric Therapy.

Vancomycin and piperacillin-tazobactam are commonly used first guns in the empiric management of critically ill patients. Current studies suggest an increased prevalence of acute kidney injury with concomitant use, however, these studies are few and limited by small sample size. The purpose of this study was to compare the prevalence of nephrotoxicity after treatment with vancomycin alone and concomitant vancomycin and piperacillin-tazobactam treatment at our institution. Concomitant vancomycin and piperacillin-tazobactam-treated patients will experience greater prevalence of nephrotoxicity compared with vancomycin-only treated patients. This was a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005 to 2009 who were not receiving hemodialysis at the time of admission. Included patients were stratified by treatment with vancomycin, vancomycin/piperacillin-tazobactam, or vancomycin/an alternative gram-negative rod (GNR) antibiotic. p values for categorical variables were computed using χ(2) while continuous variables were computed using Kruskal-Wallis. Variables deemed statistically significant (< 0.05) were included in the multivariable, log-binomial regression model. Relative risk (RR) and 95% confidence intervals (CI), and p values were computed using a generalized estimating equation (GEE) approach with robust standard errors (i.e., Huber White "sandwich variance" estimates) to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. A total of 530 patients with 1,007 episodes of infection, were treated with vancomycin (150 patients/302 episodes of infection), vancomycin/piperacillin-tazobactam (213 patients/372 episodes of infection), or vancomycin/GNR alternative (167 patients/333 episodes of infection). Patient demographics, comorbidities, sites of infection, and organisms of infection were compared among groups. After adjusting for statistically significant variables, neither vancomycin/piperacillin-tazobactam (RR = 1.1, 95% CI = 0.99-1.2; p = 0.073) nor vancomycin/GNR alternative (RR = 1.1, 95% CI = 0.98-1.2; p = 0.097) were found to be associated with an increased risk for nephrotoxicity compared with vancomycin alone. A difference in nephrotoxicity was not observed between vancomycin and vancomycin/piperacillin-tazobactam-treated patients at our institution. Concomitant use as empiric therapy is appropriate, although larger sample sizes are needed to analyze closely this relation among at-risk subsets of this population.

Vancomycin-Associated Nephrotoxicity: The Obesity Factor.

Current recommendations suggest that vancomycin dosing utilize actual rather than ideal body weight in obese patients. Thus, obese patients may be at greater risk for nephrotoxicity. The purpose of this study was to compare the incidence of nephrotoxicity in vancomycin-treated obese and lean patients at our institution, where unadjusted, actual body weight-based dosing (capped at 2 g per dose twice daily) is used. We expected obese patients to experience a greater incidence of nephrotoxicity than lean patients. This study examined a retrospective cohort of patients treated with vancomycin for gram-positive or mixed infections in our facility from 2005-2009 who were not receiving hemodialysis at the time of admission. Patients were stratified by body mass index (BMI; obese ≥30 kg/m(2) vs. lean <30 kg/m(2)). Relative risk (RR), 95% confidence intervals (CIs), and p values were computed using a generalized estimating equation to accommodate a correlated data structure corresponding to multiple episodes of infection per individual. Multivariable analysis was performed. A total of 530 patients (207 obese; 323 lean) with 1,007 episodes of infection were treated with vancomycin. Patient demographics, co-morbidities, sites of infection, and infecting organisms were similar in the two groups. Female gender (p=0.042), diabetes mellitus (DM) (p=0.018), and hypertension (HTN) (p=0.0009) were more often associated with obesity, whereas allografts (p=0.022) and peripheral vascular disease (p=0.036) were more often present in lean patients. The Acute Physiology and Chronic Health Evaluation II score >21 was the only variable associated with nephrotoxicity (p=0.039). After adjusting for statistically significant variables, obesity was found not to be associated with a greater risk of nephrotoxicity (RR=0.98; 95% CI=0.93-1.04; p=0.59). No difference in nephrotoxicity was observed between lean and obese patients treated with vancomycin at our institution.

Continuous infusion vs intermittent vancomycin in neurosurgical intensive care unit patients

PurposeTarget plasma level achievement has remained a challenge in neurosurgical intensive care unit patients receiving intravenous vancomycin. We evaluated continuous infusion (CI) and intermittent vancomycin dosing strategies in these patients. MethodsThis retrospective cohort compared CI vancomycin (target random levels, 20-30 mg/L) to intermittent vancomycin (target troughs, 15-20 mg/L) in regards to achievement of target plasma levels, nephrotoxicity, pharmacodynamic target attainment, and cost savings in 130 patients. ResultsContinuous infusion resulted in greater achievement of goal plasma concentrations at the first steady-state level (40 vs 21.5%, P = .02), more rapid achievement of goal plasma concentrations (2.04 vs 3.76 days, P < .0001), and increased time within therapeutic range (55% vs 34%, P < .0001) but no significant difference in nephrotoxicity (15.4% vs 21.5%, P = .5). Continuous infusion improved pharmacodynamic target attainment (92.3% vs 30.8%, P < .0001) and also reduced levels drawn (3.8 vs 5.7, P = .0007), dose adjustments (1.4 vs 2.4, P = .0006), days of therapy (10.4 vs 14.1, P = .01), and mean total daily dose requirements (33 vs 35.7 mg/kg, P < .0001) per patient. ConclusionsContinuous infusion appears beneficial for improving attainment of target plasma concentrations, pharmacodynamic goals, and financial burden, without increasing risk of acute kidney injury.

A randomized trial of loading vancomycin in the emergency department.

Optimizing vancomycin dosing may help eradicate bacteria while avoiding resistance. The guidelines recommend loading doses; however, there are no data to demonstrate that this may result in a more rapid achievement of therapeutic troughs. To evaluate the percentage of troughs reaching therapeutic levels at 12, 24, and 36 hours following an initial vancomycin dose of 30 mg/kg compared with 15 mg/kg. This prospective, randomized study was performed in a community academic medical center. Patients who were to receive vancomycin in the emergency department were randomized to an initial traditional dose of 15 mg/kg or a 30-mg/kg loading dose followed by 15 mg/kg every 12 hours for 3 doses. Patients weighing >120 kg or with creatinine clearances <50 mL/min were excluded. In total, 99 patients were enrolled; 12 hours after the initial dose of vancomycin, there was a significantly greater proportion of patients reaching target trough levels of 15 mg/L among the patients who received a loading dose as compared with a traditional dose (34% vs 3%, P < 0.01). This trend continued at 24 hours but was not statistically significant. At 36 hours, there was no difference in the percentage of patients reaching target levels between the 2 groups. No statistically significant difference in nephrotoxicity or adverse events among the 2 groups was demonstrated. A loading dose of 30 mg/kg of vancomycin achieved a higher percentage of therapeutic levels at 12 hours when compared with the traditional dose of 15 mg/kg, without increased nephrotoxicity or adverse events.

Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?

Iodinated contrast agents are usually classified based upon their osmolality—high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some but not all patients resulting in loss of glomerular filtration rate. Over the past 30 years, nephrotoxicity has been linked to osmolality although the precise mechanism underlying such a link has been elusive. Improvements in our understanding of the pathogenesis of nephrotoxicity and prospective randomized clinical trials have attempted to further explore the relationship between osmolality and nephrotoxicity. In this review, the basis for our current understanding that there are little if any differences in nephrotoxic potential between low and isosmolar contrast media will be detailed using data from clinical studies.

Difference in nephrotoxicity of vancomycin administered once daily and twice daily in rats

We compared the degree of nephrotoxicity of vancomycin (VCM) administered once daily and twice daily in rats. VCM was intraperitoneally administered once daily to rats at a dose of 400 mg/kg (VCM-1-treated) or administered at a dose of 200 mg/kg twice daily at 12-hour intervals (VCM-2-treated) for 7 consecutive days. Creatinine clearance was decreased more markedly in VCM-1 rats relative to VCM-2 rats, although there was no significant difference in renal accumulation of VCM between the two groups. Renal superoxide dismutase activity was lower in VCM-1 rats than that in VCM-2 rats. The magnitude of histological change in kidney tissue was in agreement with the degree of alterations in the abovementioned biochemical values. These results suggest that the nephrotoxic effect of once-daily VCM administration is more pronounced than that of the twice-daily treatment. Our findings provide fundamental evidence for the advantage in choosing a divided VCM administration to attenuate nephrotoxicity.

Higher Incidence of Acute Kidney Injury With Intravenous Colistimethate Sodium Compared With Polymyxin B in Critically Ill Patients at a Tertiary Care Medical Center

Nephrotoxicity was assessed in 173 critically ill patients receiving intravenous colistin or polymyxin B; it occurred in 60.4% and 41.8%, respectively. Further investigation is necessary to elucidate the reason for the difference in nephrotoxicity observed between the groups and to assess the impact of severity of illness and dosing/administration.

Evaluation of a vancomycin dosing nomogram based on the Modification of Diet in Renal Disease equation in intensive care unit patients

PurposeThe purpose of the study is to evaluate the effectiveness of a vancomycin nomogram using actual body weight and the Modification of Diet in Renal Disease equation to estimate renal function in intensive care unit patients. MethodsRetrospective evaluation (preimplementation group, n = 57) was conducted from March 2011 to April 2011. Prospective evaluation was conducted after nomogram implementation (postimplementation group, n = 60) from December 2011 to February 2012. ResultsThe percentage of patients with an initial vancomycin trough concentration 15 μg/mL or higher increased in the postimplementation group as compared with the preimplementation group (72% vs 39%, P = .0004). The postimplementation group also demonstrated an increase in the percentage of patients with initial trough concentration between 15 and 20 μg/mL (42% vs 19%, P = .0099), and no statistical difference in the percentage of patients with an initial trough greater than 20 μg/mL (30% vs 19%, P = .2041). There was no difference in nephrotoxicity in the postimplementation group compared with the preimplementation group (18% vs 17.5%, P = 1.0). ConclusionUse of a vancomycin nomogram increased the percentage of initial vancomycin trough concentrations 15 μg/mL or higher in intensive care unit patients and was not associated with an increased occurrence of nephrotoxicity.

Renal tolerability of iopromide and iodixanol in 562 renally impaired patients undergoing cardiac catheterisation: the DIRECT study

This multi-centre, randomised, double-blind study compared the nephrotoxicity of low-osmolar, low-viscous iopromide and iso-osmolar, high-viscous iodixanol in Chinese patients with moderate renal dysfunction, after coronary angiography or percutaneous coronary intervention (PCI). The primary endpoint was contrast-induced nephropathy (CIN) on day 3, defined as a post-dose increase in serum creatinine (SCr) of ≥50% from baseline. All patients were rigorously hydrated from six hours before intervention. In 562 evaluable patients (of 592 recruited), the contrast volume, presence of diabetes mellitus, mean baseline SCr and estimated glomerular filtration rate (eGFR) were comparable between the iopromide- and iodixanol-treated groups. SCr increases of ≥50% occurred in 1/278 (0.4%) of patients after iopromide and 1/284 (0.3%) after iodixanol. Incidences in the secondary endpoints were the following: SCr increases of ≥0.5 mg/dL, 1.4% and 0.7%, respectively; SCr increases of ≥25%, 5.4% and 2.8%; eGFR decreases of ≥25%, 3.6% and 2.5%. Only one patient showed renal failure, one week after dosing with iodixanol. All differences were statistically insignificant, in the overall collective group and in the subgroup with diabetes (n=170). With rigorous hydration, the CIN incidence was very low in patients with moderate renal dysfunction who underwent coronary angiography or PCI. No difference in nephrotoxicity was found between iopromide and iodixanol.

Moderate renal dysfunction may not require a cisplatin dose reduction: a retrospective study of cancer patients with renal impairment

The aim of this study was to assess the tolerability of cisplatin (CDDP) in patients with moderate renal dysfunction. To investigate the relationship between CDDP dose and nephrotoxicity, a retrospective chart review was conducted of patients with a creatinine clearance (Ccr) of 30-60mL/min. Subjects were classified into three groups according to the CDDP dose, as determined by the physician, and the nephrotoxicity among these groups was compared. Additionally, we investigated the correlation coefficients between maximum serum creatinine (Scr) level or minimum estimated glomerular filtration rate (eGFR) and baseline Ccr. Fifty-six patients were included in this study. Among these patients, 13 patients received 30-40mg/m(2) CDDP (group I), 18 patients received 40-70mg/m(2) (group II), and 25 patients received 70-80mg/m(2) (group III). No significant difference in nephrotoxicity was observed (median Scr 1.53, 1.61, and 1.53mg/dL, respectively), and no correlation was observed between baseline Ccr and maximum Scr (r=0.004, p=0.979) or minimum eGFR (r=0.21, p=0.119). Only two patients (3.5%) experienced grade 3 or 4 Scr elevation-one patient with a Ccr of 52.6mL/min received 60mg/m(2) CDDP, and the other patient with a Ccr of 52.1mL/min received 70mg/m(2) of CDDP. Hemodialysis was not observed. CDDP was tolerated at doses of 35-80mg/m(2) among patients with moderate renal impairment. Empiric dose reduction might create a risk of under-treatment.

Lack of differences in nephrotoxicity of intravenous bisphosphonates in metastatic breast cancer.

1122 Background: More than 50% of patients (pts) with advanced breast cancer develop bone metastases that may lead to multiple complications such as pathological fractures, bone pain, or hypercalca...

Use of a toxicity factor to explain differences in nephrotoxicity and myelosuppression among the platinum antitumour derivatives cisplatin, carboplatin and nedaplatin in rats

The platinum antitumour drugs cisplatin, carboplatin and nedaplatin differ in their toxicity. The relationships between the pharmacokinetics of these drugs and developed parameters for predicting their nephrotoxicity and myelosuppression were investigated. The drugs were administered to male Wistar rats by intravenous bolus or infusion, and linearity of pharmacokinetics, total clearance and the apparent ratio of tissue concentrations of unchanged drug to plasma concentration (Kp app) at steady state were determined. Apparent hydrolysis rates of each drug were determined in-vitro. Nephrotoxicity and myelosuppression were estimated by blood urea nitrogen (BUN) and platelet count, respectively. Tissue exposure to platinum was estimated as the product of the area under the plasma concentration-time curve for unchanged drug (AUC p), Kp app and the apparent hydrolysis rate constant (k hydrolysis), and toxicity factor was defined as the product of Kp app x k hydrolysis as an intrinsic drug parameter. The relationship between AUC p x toxicity factor and BUN fitted well to an Emax model. In bone marrow, this function was also correlated with platelet count. In summary, the product of AUC p x toxicity factor is a factor determining the pharmacokinetics of platinum drug-induced nephrotoxicity and myelosuppression in rats, and this toxicity factor may be a useful parameter for predicting the degree of toxicity of platinum antitumour compounds.