共查询到20条相似文献,搜索用时 11 毫秒
1.
Carlo L. Bello May Garrett Laurie Sherman John Smeraglia Bob Ryan Melvin Toh 《Cancer chemotherapy and pharmacology》2010,66(4):699-707
This study evaluated the effect of hepatic impairment on the pharmacokinetics of sunitinib and its active metabolite, SU12662. This open-label study enrolled subjects with normal hepatic function (n = 8), mild (Child–Pugh [CP]-A; n = 8), or moderate (CP-B; n = 8) hepatic impairment. Subjects received sunitinib 50 mg as a single oral dose. Mild or moderate hepatic impairment did not significantly alter sunitinib, SU12662, or total drug (TD) systemic exposure. In subjects with normal hepatic function, mild, or moderate hepatic impairment, respectively, TD AUC0–∞ was 1,938, 2,002, and 1,999 ng h/ml, TD AUC0–last was 1,913, 1,956, and 1,958 ng h/ml, and TD C max was 26.0, 27.3, and 26.7 ng/ml. There were no other notable pharmacokinetic differences and sunitinib was well tolerated. The pharmacokinetic findings of this study do not indicate a need to adjust the currently approved starting dose of sunitinib (50 mg daily on Schedule 4/2) for cancer patients with mild to moderate liver impairment. 相似文献
2.
L. A. Devriese P. O. Witteveen S. Marchetti M. Mergui-Roelvink L. Reyderman J. Wanders A. Jenner G. Edwards J. H. Beijnen E. E. Voest J. H. M. Schellens 《Cancer chemotherapy and pharmacology》2012,70(6):823-832
Purpose
The aim of this study was to determine the plasma pharmacokinetics of eribulin mesylate in patients with solid tumors with mild and moderate hepatic impairment.Patients and methods
A phase I, pharmacokinetic study was performed in patients with advanced solid tumors and normal hepatic function or Child-Pugh A (mild) or Child-Pugh B (moderate) hepatic impairment. Treatments were given on day 1 and 8 of a 21-day cycle and consisted of 1.4, 1.1 and 0.7?mg/m2 eribulin mesylate, for normal hepatic function, Child-Pugh A and B hepatic impairment, respectively. Also safety and anti-tumor activity were determined.Results
Hepatic impairment increased exposure to eribulin. In patients with Child-Pugh A (N?=?7) and Child-Pugh B (N?=?5), mean dose-normalized AUC0?C?? was 1.75-fold (90?% confidence intervals (CI): 1.16?C2.65) and 2.48-fold (90?% CI: 1.57?C3.92) increased, respectively, compared with patients who have normal function (N?=?6). The most frequently reported treatment-related events were alopecia (12/18) and fatigue (7/18) and these were observed across all groups. Nine patients (50?%) had stable disease as best response.Conclusions
A reduced dose of 1.1 and 0.7?mg/m2 of eribulin mesylate is recommended for patients with Child-Pugh A or B hepatic impairment, respectively. 相似文献3.
Narayana I. Narasimhan David J. Dorer Jeffrey Davis Christopher D. Turner Thomas C. Marbury Daryl Sonnichsen 《Cancer chemotherapy and pharmacology》2014,74(2):341-348
Purpose
This study evaluated the effects of chronic hepatic impairment on the single-dose pharmacokinetics (PK) of the tyrosine kinase inhibitor ponatinib.Methods
Subjects (n = 16) had Child-Pugh class A (mild, n = 6), B (moderate, n = 6), or C (severe, n = 4) hepatic impairment and were matched with healthy controls (n = 8). Each subject received a single oral dose of ponatinib 30 mg under fasting conditions, and PK parameters were assessed in blood samples collected through 96 h post-dose.Results
Ponatinib maximum plasma concentrations (C max) were observed after 5–6 h in Child-Pugh A, Child-Pugh B, and healthy subjects, and after ~3 h in Child-Pugh C subjects. The estimated % geometric mean ratios for C max, area under the plasma concentration–time curves from time zero to last observation (AUC0–t ) and to infinity (AUC0–∞) suggested a slightly lower exposure in Child-Pugh B (61.4, 89.1, and 90.6 %, respectively) and Child-Pugh C subjects (62.8, 77.1, and 79.4 %) versus healthy subjects. Child-Pugh A subjects had similar estimated % geometric mean ratio for C max (106.7 %), and slightly greater estimated % geometric mean ratios for AUC0–t (133.0 %) and AUC0–∞ (122.8 %), versus healthy subjects. Mean elimination half-life was extended in subjects with hepatic impairment (43–47 vs 36 h). Ponatinib was generally well tolerated. A single serious AE (pancreatitis) in the Child-Pugh C group resolved with treatment.Discussion
As no major differences in ponatinib single-dose PK were observed in patients with hepatic impairment versus healthy subjects, a reduction of ponatinib starting dose in these patients is not necessary, but caution is recommended when administering ponatinib to these patients. 相似文献4.
Dan C. Dimmitt Michael B. Cramer Anther Keung Thangam Arumugham Scott J. Weir 《Cancer chemotherapy and pharmacology》1999,43(2):126-132
Purpose: Dolasetron is a selective 5-HT3 receptor antagonist. The purpose of this study was to determine the effect of cimetidine and rifampin on the steady-state
pharmacokinetics of orally administered dolasetron and its active reduced metabolite, hydrodolasetron. Methods: A group of 18 healthy men (22 to 44 years old) were randomized to receive each of the following three treatments in a three-period
crossover design: 200 mg dolasetron daily (treatment A); 200 mg dolasetron daily plus 300 mg cimetidine four times daily (treatment
B); or 200 mg dolasetron daily plus 600 mg rifampin daily (treatment C). Each study period was separated by a 14-day washout
period. Serial blood samples were collected before the first dose (baseline) on day 1 and at frequent intervals up to 48 h
after the morning dose on day 7 for quantification of dolasetron and its metabolites, hydrodolasetron (both isomers), 5′OH
hydrodolasetron, and 6′OH hydrodolasetron. Serial urine samples were also collected at baseline and during the periods 0–24
and 24–48 h following the morning dose on day 7, and analyzed for dolasetron and its metabolites. Results: Plasma and urine dolasetron concentrations were below quantifiable concentrations for all three treatments. Mean steady-state
area under the plasma concentration-time curve (AUCss(0–24)) of hydrodolasetron increased by 24%, mean apparent clearance (CLapp,po) decreased by 19%, and maximum plasma hydrodolasetron concentration (Cmax,ss) increased by 15% when dolasetron was coadministered with cimetidine. When dolasetron was given with rifampin, mean hydrodolasetron
AUCss(0–24) decreased by 28%, CLapp,po increased by 39%, and hydrodolasetron Cmax,ss decreased by 17%. Small differences were found in mean tmax (0.7 to 0.8 h), CLr (2.0 to 2.6 ml/min per kg), and t1/2 (7.4 to 8.8 h) for hydrodolasetron between treatment periods. Approximately 20% and 2% of the dolasetron dose were excreted
in urine as the R(+) isomer and S(−) isomer of hydrodolasetron, respectively, across all three treatments. Dolasetron mesylate was well tolerated in this study
during all three treatment periods, with the highest incidence of adverse events reported during the control period when dolasetron
mesylate was given alone. Conclusion: Based on the small changes in the pharmacokinetic parameters of dolasetron and its active metabolites, as well as the favorable
safety results, no dosage adjustments for dolasetron mesylate are recommended with concomitant administration of cimetidine
or rifampin.
Received: 10 February 1998 / Accepted: 1 June 1998 相似文献
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6.
Richat Abbas Stephan Chalon Cathie Leister Myriam El Gaaloul Daryl Sonnichsen 《Cancer chemotherapy and pharmacology》2013,71(1):123-132
Purpose
Bosutinib, a dual Src/Abl kinase inhibitor in development for treatment of chronic myeloid leukemia, is primarily metabolized by the CYP3A4 hepatic enzyme. This study evaluated the pharmacokinetics and safety of bosutinib in patients with chronic hepatic impairment and matched healthy subjects.Methods
Hepatically impaired patients were aged 18–65 years and of Child-Pugh classes A, B, or C; healthy subjects were matched by age, sex, body mass index, and smoking habits. A single oral dose of bosutinib 200 mg was administered on day 1 within 5 min after completion of breakfast.Results
Compared with healthy subjects (n = 9), maximal plasma concentration (C max) and area under the curve increased 2.42-fold and 2.25-fold in Child-Pugh A (n = 6), 1.99-fold and 2.0-fold in Child-Pugh B (n = 6), and 1.52-fold and 1.91-fold in Child-Pugh C patients (n = 6). Time to C max decreased from 4 h in healthy subjects to 2.5, 2.0, and 1.5 h in Child-Pugh A, B, and C patients, respectively; the elimination half-life increased from 55 h in healthy subjects to 86, 113, and 111 h in Child-Pugh A, B, and C patients. Bosutinib oral clearance was lower in hepatically impaired patients compared with healthy subjects. Frequently reported adverse events included prolonged QTc interval (37.0 %, n = 10), nausea (11.1 %, n = 3), and vomiting (7.4 %, n = 2).Conclusions
A single oral dose of bosutinib 200 mg showed acceptable tolerability in healthy subjects and in patients with mild, moderate, or severe chronic hepatic impairment. 相似文献7.
8.
Baur M Drescher A Gneist M Dittrich C Jaehde U 《Cancer chemotherapy and pharmacology》2008,61(1):97-104
Purpose Data are lacking on the pharmacokinetics of oxaliplatin in patients with severe hepatic dysfunction. The aim of this study
was to determine the pharmacokinetic parameters of platinum after administration of oxaliplatin in cancer patients with severe
hepatic impairment due to extended metastases into the liver.
Patients and methods Two female breast cancer patients and one male colon cancer patient were treated with oxaliplatin monotherapy at 130 mg/m2
given as a 3-h intravenous infusion. The patients exhibited bilirubin concentrations of 9.6, 22.5 and 41.1 mg/dl indicating
severe hepatic dysfunction. Serial blood samples were collected immediately before treatment, and at fixed intervals up to
27 h after start of therapy. Platinum concentrations in plasma, ultrafilterable plasma, and whole blood were determined using
a validated flameless atomic absorption spectrometry (FAAS) method. Pharmacokinetic data analysis was performed assuming a
two-compartment model. Individual pharmacokinetic parameters were compared with a reference population with normal hepatic
function.
Results The area under the curve (AUC from 0 to infinity) as well as the elimination half-life of platinum in ultrafilterable plasma
were substantially increased and clearance accordingly decreased in the three patients with severe hepatic dysfunction. In
plasma and whole blood, the deviations from the reference population were less pronounced. However, partial AUC from 0 up
to 2 h after end of infusion reflecting better the exposure with cytotoxic platinum species was not different or only slightly
altered. Moreover, no acute oxaliplatin-associated neurotoxicity was observed.
Conclusions The comparable platinum exposure early after administration in conjunction with the lack of acute toxicity do not support
a dose reduction of oxaliplatin in patients with markedly elevated bilirubin concentrations. However, a larger number of patients
must be examined before valid dose recommendations can be derived. 相似文献
9.
Pharmacokinetics and antitumor effects of mitoxantrone after intratumoral or intraarterial hepatic administration in rabbits 总被引:2,自引:0,他引:2
Luis H. Ramirez Zhongxin Zhao Philippe Rougier Caroline Bognel Radan Dzodic Gilles Vassal Patrice Ardouin Alain Gouyette J.-N. Munck 《Cancer chemotherapy and pharmacology》1996,37(4):371-376
The intratumoral (i.t.) delivery of anticancer drugs aims at controlling tumor growth and thereby provides palliative treatment
for liver neoplasms. Mitoxantrone is a good candidate for local or regional administration because (1) its metabolism is mainly
hepatic, (2) it has a steep dose-response curve for multiple solid tumors, and (3) its fixation in tissues is sustained without
vesicant effects after extravasation. We compared the tolerance, pharmacokinetics, and antitumor effects of mitoxantrone on
hepatic VX2 tumors in rabbits treated with i.t. intraarterial hepatic (i.a.h.) or i.v. mitoxantrone, i.t. ethanol; or i.t.
0.9% NaCl and in control animals. Tumor growth rates (TGRs) were evaluated at 9 days after treatment. Myelosuppression was
the limiting toxicity of i.v. mitoxantrone at 1.5 mg/kg (maximal tolerated dose, MTD), but neither i.t. nor i.a.h. administration
led to hematologic toxicity at the same dose. The mitoxantrone retained in tumors after i.t. administration was seen as blue-stained
areas of complete necrosis according to histologic analysis. Pharmacokinetic parameters showed a significantly decreased systemic
exposure to the drug after both regional treatments, although the i.a.h. route appeared to have an edge over the i.t. route.
TGRs were significantly reduced after i.t. mitoxantrone (81±62%), i.a.h. mitoxantrone (337±110%), and i.t. ethanol treatments
(287±117%) as compared with control values (886±223%; p<0.01). Treatment with i.v. mitoxantrone (816±132%) had no antitumor effect, nor did NaCl injections (868±116%). Mitoxantrone
given i.t. induced the highest antitumor effects, resulting in a 3.5-fold reduction in TGRs as compared with i.a.h. mitoxantrone
and i.t. ethanol treatments (p<0.02). Treatment with i.t. mitoxantrone provided efficient antitumor therapy without producing major side effects. This method
should be considered as palliative treatment for nonresectable liver tumors and other localized malignancies.
Received: 13 December 1994/Accepted: 6 June 1995 相似文献
10.
Dehua Zhao Xiaoqing Long Hongying Fan Jisheng Wang 《American journal of cancer research》2022,12(11):4892
Immune checkpoint inhibitors (ICIs) have become the cornerstone in treating many solid and hematological cancers. The ICIs, including anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), anti-programed cell death 1 (PD-1), and anti-programed death-ligand 1 (PD-L1) monoclonal antibodies, have significantly improved the prognosis of cancer patients. Meanwhile, the incidence of hepatic or renal impairment in cancer patients is increasing. However, data about the efficacy and safety of ICIs in patients with hepatic or renal impairment are limited. In this review, we characterize and summarize the pharmacokinetics (PK) of ICIs as well as the effects of hepatic or renal function on the PK of ICIs, and provide specific recommendations for clinicians when prescribing ICIs in patients with hepatic or renal impairment. 相似文献
11.
Lathia C Fleming GF Meyer M Ratain MJ Whitfield L 《Cancer chemotherapy and pharmacology》2002,50(2):121-126
PURPOSE: The purpose of this study was to determine the pharmacokinetic parameters of pentostatin in renally impaired patients in order to establish dosing guidelines for this population. METHODS: Pentostatin doses were administered as 15-min intravenous infusions to patients based on their measured creatinine clearance (CLcr) as follows. Patients with normal renal function (NRF), defined as CLcr >60 ml/min, received 4 mg/m(2) repeated every14 days. Patients with impaired renal function (IRF) included those with CLcr 41-60 ml/min who received 3 mg/m(2) and those with CLcr 21-40 ml/min who received 2 mg/m(2), also repeated every 14 days. Heparinized plasma samples were collected during drug infusion and out through 96 h after dosing, except in two patients in whom sampling was extended to 144 h after dosing. Urine sampling extended to 96 h after dosing, and all samples were analyzed by a validated enzyme immunoassay for pentostatin concentrations. RESULTS: Enrolled in the study were 13 patients (7 IRF and 6 NRF), of whom 12 contributed samples for pharmacokinetic analysis. Median baseline CLcr values were 71.5 ml/min for NRF patients and 44 ml/min for IRF patients. Following the end of intravenous infusion, pentostatin plasma concentrations declined biexponentially with time. In some patients there was a transient increase in pentostatin equivalents 2 to 4 h after dosing. There was a good correlation between measured CLcr and pentostatin total plasma clearance. The AUC(0- infinity ) values seen in IRF patients, at lower doses, were within the range of the AUC(0- infinity ) values seen in patients with normal CLcr. Toxicities observed in the two groups of patients were similar. CONCLUSIONS: The pentostatin doses used in the study appear to be appropriate for administration to cancer patients with varying degrees of renal impairment. 相似文献
12.
M D'Incalci C Rossi M Zucchetti R Urso F Cavalli C Mangioni Y Willems C Sessa 《Cancer research》1986,46(5):2566-2571
Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Clp), volume of distribution (Vd), and elimination half-life (t1/2 beta) of VP16 were, respectively, 22.8 +/- 1.0 (SE) ml/min/m2, 11.4 +/- 0.8 liters/m2, and 5.6 +/- 0.4 h. In patients with renal insufficiency Clp was 12.8 +/- 1.1 ml/min/m2, Vd was 20.8 +/- 4.9 liters/m2, and t1/2 beta was 19.2 +/- 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Clp and creatinine clearance. In 12 of 15 patients with abnormal liver tests Clp, Vd, and t1/2 beta were, respectively, 27.9 +/- 2.7 ml/min/m2, 12.4 +/- 1.5 liters/m2, and 5.4 +/- 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t1/2 beta values were similar (5.1, 4.4, and 5.1 h) whereas Clp values (320, 87, and 96 ml/min/m2) and Vd values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 Vd and Clp values found in a subset of patients with liver impairment require further elucidation. 相似文献
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14.
Jannuzzo MG Poggesi I Spinelli R Rocchetti M Cicioni P Buchan P 《Cancer chemotherapy and pharmacology》2004,53(6):475-481
Purpose Two studies were conducted to compare the pharmacokinetics and tolerability of exemestane in postmenopausal subjects with various degrees of impairment of hepatic or renal function with those in healthy postmenopausal subjects.Methods All subjects were postmenopausal females. In study 1, nine subjects had normal hepatic function (Child-Pugh grade A), and nine had moderately (grade B) and eight severely (grade C) impaired hepatic function. In study 2, six subjects had normal renal function, and six moderately (creatinine clearance, CrCL, 30–60 ml/min per 1.73 m2) and seven severely (CrCL <29 ml/min per 1.73 m2) impaired renal function. Each subject took a single oral dose of 25 mg exemestane. Samples of plasma (to 168 h after dosing) and urine (to 72 h in study 1, or 96 h in study 2) were taken for pharmacokinetic analysis. Safety and tolerability were assessed by monitoring vital signs, laboratory safety tests, ECG and adverse events.Results Exposure to exemestane was increased two- to threefold in patients with hepatic impairment. Thus, the geometric mean AUC0– values were 41.71 (90% CI 32.2 to 54.0), 99.02 (76.5 to 128.2) and 118.59 ng·h/ml (90.2 to 156.0) in healthy subjects, and in patients with moderate and severe hepatic impairment, respectively (P<0.01). Cmax also increased twofold. Compared with healthy subjects, patients with hepatic impairment had lower apparent oral clearance and apparent volume of distribution of exemestane. Renal impairment was also associated with two- to threefold increases in AUC0–: 34.64 (90% CI 23.9 to 50.2), 94.10 (64.9 to 136.4) and 65.52 ng·h/ml (46.5 to 92.4) in healthy subjects, and in patients with moderate and severe hepatic impairment, respectively (P<0.05). Cmax did not change significantly. Apparent oral clearance was directly correlated with CrCL (r2=0.43). Exemestane was tolerated well, with no safety concerns.Conclusions Oral clearance of exemestane was reduced in the presence of significant hepatic or renal disease. However, in view of the relatively large safety margin and the mild nature of the side effects of exemestane, the therapeutic implications of these changes in pharmacokinetics are considered minor and of no clinical significance. 相似文献
15.
Min Hee Hong MD Seong Gu Heo PhD Yun-Gyoo Lee MD PhD Hyo Song Kim MD PhD Keon Uk Park MD PhD Hoon-Gu Kim MD PhD Yoon Ho Ko MD PhD Ik-Joo Chung MD PhD Young Joo Min MD PhD Min Kyoung Kim MD PhD Kyu Ryung Kim PhD Jinseon Yoo MS Tae-Min Kim MD PhD Hye Ryun Kim MD PhD Byoung Chul Cho MD PhD 《Cancer》2020,126(20):4521-4531
16.
《Journal of Geriatric Oncology》2022,13(5):635-643
BackgroundDementia and cancer are both more common in adults as they age. As new cancer treatments become more popular, it is important to consider how these treatments might affect older patients. This study evaluates metastatic renal cell carcinoma (mRCC) as a risk factor for older adults developing mild cognitive impairment or dementia (MCI/D) and the impact of mRCC-directed therapies on the development of MCI/D.MethodsWe identified patients diagnosed with mRCC in a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2015 and matched them to non-cancer controls. Exclusion criteria included age < 65 years at mRCC diagnosis and diagnosis of MCI/D within the year preceding mRCC diagnosis. The main outcome was time to incident MCI/D within one year of mRCC diagnosis for cases or cohort entry for non-cancer controls. Cox proportional hazards models were used to measure associations between mRCC and incident MCI/D as well as associations of oral anticancer agent (OAA) use with MCI/D development within the mRCC group.ResultsPatients with mRCC (n = 2533) were matched to non-cancer controls (n = 7027). mRCC (hazard ratio [HR] 8.52, p < .001), being older (HR 1.05 per 1-year age increase, p < .001), and identifying as Black (HR 1.92, p = .047) were predictive of developing MCI/D. In addition, neither those initiating treatment with OAAs nor those who underwent nephrectomy were more likely to develop MCI/D.ConclusionsPatients with mRCC were more likely to develop MCI/D than those without mRCC. The medical and surgical therapies evaluated were not associated with increased incidence of MCI/D. The increased incidence of MCI/D in older adults with mRCC may be the result of the pathology itself or risk factors common to the two disease processes. 相似文献
17.
目的 观察多瑞吉 (芬太尼贴剂 )治疗晚期癌痛患者的镇痛效果和不良反应。方法 4 2例晚期癌痛患者 ,治疗前均为中、重度疼痛 ,使用多瑞吉镇痛治疗 ,每 2 4小时评定疗效一次 ,至少观察 15天。结果 全组完全缓解 5例 (11.9% ) ,明显缓解 31例 (73.8% ) ,总有效率为 85 .7%。不良反应主要为便秘、恶心呕吐、皮肤瘙痒及嗜睡等 ,发生率低。结论 多瑞吉治疗中、重度癌痛 ,镇痛效果好 ,不良反应小 ,值得临床进一步推广应用。 相似文献
18.
Shaiju K Vareed Madhuri Kakarala Mack T Ruffin James A Crowell Daniel P Normolle Zora Djuric Dean E Brenner 《Cancer epidemiology, biomarkers & prevention》2008,17(6):1411-1417
BACKGROUND: Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited. METHODS: This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a one-compartment absorption and elimination model. RESULTS: Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only one subject had detectable free curcumin at any of the 14 time points assayed, but curcumin glucuronides and sulfates were detected in all subjects. Based on the pharmacokinetic model, the area under the curve for the 10 and 12 g doses was estimated (mean +/- SE) to be 35.33 +/- 3.78 and 26.57 +/- 2.97 mug/mL x h, respectively, whereas C(max) was 2.30 +/- 0.26 and 1.73 +/- 0.19 mug/mL. The T(max) and t(1/2) were estimated to be 3.29 +/- 0.43 and 6.77 +/- 0.83 h. The ratio of glucuronide to sulfate was 1.92:1. The curcumin conjugates were present as either glucuronide or sulfate, not mixed conjugates. CONCLUSION: Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma. 相似文献
19.
A Krarup-Hansen K Wassermann S N Rasmussen M Dalmark 《Acta oncologica (Stockholm, Sweden)》1988,27(1):25-30
The common side effects of doxorubicin (DOX) treatment, i.e. vomiting and diarrhoea, would be expected to alter the pharmacokinetics of DOX in man, the efficacy of treatment, and further aggravate the side effects through acid/base disturbances. The pharmacokinetics were therefore investigated in 4 anthracycline naive females with advanced mammary carcinoma in 2 series of DOX monotherapy 70 mg/m2 administered with an interval of 4 weeks between the treatments. Sequential loading either with acid or base was instituted 2 days before and continued for 2 days after DOX infusion. Median urine pH was 5.0 or 8.0, and median arterial blood pH 7.30 or 7.43 respectively. Plasma and urine samples were analyzed by high performance liquid chromatography (HPLC). No difference was seen between the acid and alkaline condition for DOX or doxorubicinol with regard to clearance from blood plasma, area under the curve, renal clearance, renal drug clearance/renal creatinine clearance. Thus moderate acid/base metabolic disturbances did not alter the pharmacokinetics of DOX up to 48 h after DOX infusion. 相似文献