Abstract:
BACKGROUND AND OBJECTIVE:The antitumor activity and toxicity of doxorubicin are potentiated and attenuated by calcitriol, respectively. Potentially, calcitriol can be combined with doxorubicin for clinical benefit in chemotherapy. To gain insight into the interaction between doxorubicin and calcitriol, proposed for combined use in cancer treatment, we studied calcitriol's effect on the plasma pharmacokinetics, tissue distribution and excretion of doxorubicin in female and male mice. METHODS:The control and calcitriol-treated groups, including an equal number of both sexes, received corn oil and calcitriol (2.5 μg/kg), respectively, intraperitoneally every other day for 8 days. At day 9, doxorubicin was administered intraperitoneally at a 6 mg/kg dose to each group. Doxorubicin concentrations in biologic specimens were determined by a high-performance liquid chromatographic-ultraviolet detector and analyzed using a non-compartmental model. RESULTS:The plasma pharmacokinetics of doxorubicin were similar in the control and calcitriol-treated groups. While calcitriol did not alter the area under the plasma concentration-time curves (AUCs) and peak concentrations (Cmax) of doxorubicin in the small intestine and testis, it significantly reduced the AUCs and Cmax of doxorubicin in the lung, kidney, spleen, liver, stomach and ovaries. However, calcitriol increased the AUCs and Cmax of doxorubicin in the heart of females, brain of males and duodenum content and vitreous humor of female and male mice. The percent cumulative urine and fecal amounts of doxorubicin in calcitriol-treated mice were higher at 89.23% and 29.37% for female mice and 118.57% and 41.65% for male mice than those in the control mice, respectively. CONCLUSIONS:The tissue concentrations and excretion of doxorubicin in both female and male mice are influenced by calcitriol without changes in the plasma pharmacokinetics. The results from this study can provide insights to help obtain the optimal drug combination effects of doxorubicin with calcitriol in cancer treatment.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Durna Corum D,Uney Kdoi
10.1007/s13318-020-00632-6subject
Has Abstractpub_date
2020-10-01 00:00:00pages
653-664issue
5eissn
0378-7966issn
2107-0180pii
10.1007/s13318-020-00632-6journal_volume
45pub_type
杂志文章abstract::Monoclonal antibodies are capable of modulating drug metabolising enzymes resulting in unexpected plasma concentrations of a drug when given concomitantly. Therefore plasma concentration of paclitaxel (PTX) and its metabolites has been monitored in 10 patients with advanced breast cancer during treatment with PTX alon...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190613
更新日期:2005-07-01 00:00:00
abstract::This study examined the effects of the absorption enhancers, acylcarnitines, on efflux transporting systems, including P-glycoprotein (P-gp) and other efflux transporters, and elucidated the importance of acyl chain length and the concentration of acylcarnitine on the activity of efflux transport. The effects of two a...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-010-0001-1
更新日期:2010-09-01 00:00:00
abstract::The compound 4-amino-3-(3'-methoxycarbonyl-2'-thioureido) benzophenone has shown promise as a prodrug of the anthelmintic mebendazole. The compound is stable in acid and neutral media and is rapidly hydrolysed in base. An HPLC assay procedure for mebendazole, the prodrug and their known or expected metabolites and deg...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188765
更新日期:1983-10-01 00:00:00
abstract::The evaluation of new intranasal medications requires the development of in vitro cell model suitable for high-throughput screening studies. The aim of a pharmacological model is to closely mimic the barrier properties of human nasal mucosa that will influence drug pharmacokinetics. In this context, the human nasal ce...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s13318-017-0426-x
更新日期:2018-02-01 00:00:00
abstract::Hyaluronic acid (HA), is a high molecular weight (HMW) glucosaminoglycan with significant acitivity, and which influences a number of physiological and pathological processes such as tumorogenesis, arthritis, etc. The aim of this study was to determine the difference in the biodistributional pathways of 111In-labeled ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191112
更新日期:2008-07-01 00:00:00
abstract::The influence of phenobarbital pretreatment on liver concentration of digitoxin and its metabolites was studied in guinea-pigs after i.p. administration of the cardiac glycoside. During the first hour an increase in liver uptake was observed in pretreated animals. The differences detected in the hepatic subcellular di...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189562
更新日期:1982-01-01 00:00:00
abstract::The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetopr...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190149
更新日期:1992-07-01 00:00:00
abstract::The purpose of this study was to determine the distribution of cyclosporin A (CsA) in various ocular fluids and tissues in the rabbit by two routes of administration. CsA was administered to two groups of two rabbits either by intramuscular route at a dose of 25 mg/kg/day or by local route using eyedrops, at a dose of...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::The aim of the current investigation was to assess the ability GFJ to modulate the pharmacokinetic profile of paracetamol following single or repeated administrations of GFJ in Sprague-Dawley rats. Diclofenac and carbamazepine were both used as positive controls. Rats received single GFJ or single distilled water dose...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-014-0251-4
更新日期:2016-04-01 00:00:00
abstract::Diabetes mellitus is becoming an increasingly prevalent disease that concerns patients and healthcare professionals worldwide. Among many anti-diabetic agents in clinical uses, numerous reports are available on their altered pharmacokinetics because of changes in the expression of drug transporters and metabolic enzym...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s13318-015-0306-1
更新日期:2016-06-01 00:00:00
abstract::The disposition of a single 80 mg/kg injection of quinine base was compared in control and Plasmodium berghei-infected mice. Pharmacokinetic parameters were determined on repeated whole blood samples from caudal vein (experiment 1) and quinine distribution was evaluated in tissues and blood fractions from mice sacrifi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190862
更新日期:2003-01-01 00:00:00
abstract::The technique of differential display reverse transcription-polymerase chain reaction (ddRT-PCR) has been used to produce unique profiles of up-regulated and down-regulated gene expression in the liver of male Wistar rats following short term exposure to the non-genotoxic hepatocarcinogens, phenobarbital and WY-14,643...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190966
更新日期:1997-10-01 00:00:00
abstract::We studied the hepatic handling of bromosulfophthalein in healthy rabbits with hepatic coccidiosis 28 days after an experimental infection with sporulated oocysts of Eimeria stiedai, an experimental model of liver disease histopathologically resembling primary biliary cirrhosis in man. A pharmacokinetic study of the r...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190121
更新日期:1990-01-01 00:00:00
abstract::The aim of this work was to use radiopharmaceuticals such as technetium (99mTc) and indium (DTPA-Ca111In) to visualize, with a gamma-camera, the disintegration area and time of 3 types of enteric coated hard gelatin capsules (obtained by 3 different preparation processes) and thus, to verify that they are really resis...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/BF03188829
更新日期:1994-04-01 00:00:00
abstract::The effect of exogenous coenzyme Q10 (CoQ10) on the pharmacokinetic profiles and biliary excretion of doxorubicin and its main metabolites, doxorubicinol and doxorubicinolone, was investigated in rats. No statistically significant changes in the pharmacokinetic parameters of doxorubicin was observed following the intr...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190456
更新日期:2002-07-01 00:00:00
abstract::Torcetrapib was the lead candidate belonging to the class of cholesteryl ester transfer protein (CETP) inhibitor which was being developed for the management of cardiovascular risk factors by raising HDL. The availability of pharmacokinetic parameters (clearance: CL/F, volume of distribution: Vd/F, elimination rate co...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191385
更新日期:2009-01-01 00:00:00
abstract::Hepatic distributional volumes were investigated in the in situ perfused rat liver. Perfusion experiments were conducted using Krebs bicarbonate buffer delivered via the portal vein in single-pass mode at a total flow rate of 15 mL/min. A bolus dose of normal erythrocytes (RBC, vascular marker) and Evans blue (EB, ext...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190469
更新日期:2006-10-01 00:00:00
abstract::Release rates from intramuscular and intra-adipose injection sites are dependent upon several including injection depth. Little is known about the relationship between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to investigate to wh...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::We retrospectively analyzed amikacin pharmacokinetics in 19 critically ill patients who received amikacin intravenously. Fourteen subjects (577 serum amikacin concentrations, 167 urine measurements) were studied to obtain data for population modeling, while 5 patients (267 serum amikacin concentrations, 68 urine measu...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190009
更新日期:1999-01-01 00:00:00
abstract::The pharmacokinetics of amiodarone was studied after single and multiple dosing in two groups of male Wistar and Albino rats. The first group (40 rats) received a single intraperitoneal (i.p.) dose of amiodarone (100 mg/kg) and 4 rats sacrificed 1, 2, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dosing. The second group...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03192314
更新日期:2000-07-01 00:00:00
abstract::Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluatin...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190181
更新日期:1993-10-01 00:00:00
abstract::Metoprolol Oros tablets were designed to deliver their drug content as a constant rate over a period of time longer than that currently recorded with slow-release dosage forms. The bioavailability of 7/95, 14/190 and 21/285 Oros tablets was compared to that of either 100 mg conventional or 200 mg slow-release Lopresor...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188865
更新日期:1994-10-01 00:00:00
abstract::Intermittent inhalation exposure of adult male rats to dichloromethane, trichloroethylene, 1,1,1-trichloroethane, perchloroethylene or to a combination of trichloroethylene and 1,1,1-trichloroethane for 5 days, for 6 h daily, induced significantly different accumulations of solvent molecules in the body. Adipose tissu...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/BF03189473
更新日期:1981-01-01 00:00:00
abstract::The disposition kinetics of the N-oxide of picobenzide were studied after administration to rabbits at a bolus dose of 30 mg/kg of picobenzide intravenously. The biotransformation process fits a first-order kinetic process, and the metabolite shows good access capacity to the peripheral compartment. The N-oxide of pic...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190837
更新日期:1989-01-01 00:00:00
abstract::Recent evidences suggest that genetic CYP2C19 polymorphism plays a role in the development of treatment resistance for clopidogrel's antiplatelet therapy. This short communication puts forward some strategies that could be potentially used to overcome the genetic polymorphism associated hurdles. While there is some es...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191165
更新日期:2009-07-01 00:00:00
abstract::The kinetics of five cisplatin analogs binding to human plasma fractions possessing a molecular weight greater than 50,000 daltons were studied. Each drug solution in plasma ultrafiltrate or phosphate buffer (pH = 7.4, mu = 0.154) was mixed with human plasma and filterable platinum concentrations were measured versus ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189700
更新日期:1985-01-01 00:00:00
abstract::The present study was carried out to find the in vivo performance of guar gum-based colon-targeted tablets of metronidazole as compared to an immediate release tablets in human volunteers. Six healthy volunteers participated in the study and a crossover design was used. Blood samples were obtained at different time in...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/BF03220181
更新日期:2003-10-01 00:00:00
abstract::Herbal medicinal products have to meet comparable standards concerning the assessment of efficacy, safety and (bio)pharmaceutical quality as chemically defined synthetic drugs. However, these requirements are not fulfilled for many herbal products so far, particularly regarding in vitro dissolution and in vivo bioavai...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190057
更新日期:2000-01-01 00:00:00
abstract::The purpose of the study was to investigate the factors upon which the first order rate constant depends in order to assess the impact on the body-drug concentration when it changes throughout a treatment. A reasoning for linking the first order rate constants with several factors in a multiplicative way was proposed ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190573
更新日期:2004-01-01 00:00:00
abstract::Blood loss during cesarean section was calculated based on post-operative decrement of hemoglobin (Hb) and hematocrit (Hct) level. The model used for pregnant women was previously validated for non-pregnant women who underwent gynecological surgery. 1,068 pregnant women who underwent cesarean section and 517 women who...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0042-0
更新日期:2011-09-01 00:00:00