SEARCH · PubMed Health

Results for “SULFINPYRAZONE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

PubMed2002

Pharmacological characterization of the ATP-dependent low K(m) guanosine 3',5'-cyclic monophosphate (cGMP) transporter in human erythrocytes.

The efflux pump for cGMP has been shown to be an ATP-energized multiorganic anion transporter. The present study was performed to extend the knowledge of the pharmacological characteristics of this efflux pump. Inside-out vesicles prepared from fresh blood were incubated with [3H]-cGMP (1 microM) with or without various concentrations of competitors for 120min at 37 degrees. The tested compounds could be divided in four groups: one with high affinity (K(i) < 5 microM), a second with moderate affinity (K(i): 5-50 microM), a third with low affinity (K(i): 0.1-5mM) and the fourth with extremely low or no affinity at all. With the mean K(i)-values given in parenthesis, the high affinity group consisted of mifepristone (0.2 microM), zaprinast (0.35 microM), dipyridamole (0.35 microM), estradiol 3-beta-glucuronide (0.42 microM), genistein (0.43 microM), estradiol 17-beta-glucuronide (0.47 microM), onapristone (1.3 microM), progesterone (1.7 microM) and sildenafil (3.6 microM). The inhibitors with medium affinity were estradiol (8 microM), sulfinpyrazone (13 microM), daunorubicin (23 microM), megestrol acetate (26 microM), doxorubicin (28 microM), 6-thioguanine (28 microM) and 6-thioguanosine-5'-monophosphate (32 microM). The low affinity group comprised 6-TIMP (220 microM), 6-methylmercaptopurine (MMP) (220 microM), vincristine (270 microM), medroxyprogesterone (680 microM), para-aminohippurate (PAH) (1.9mM) and taurocholate (2.2mM). No or minimal effect was seen in the presence of 6-mercaptopurine (6-MP), methotrexate, 9-(2-phosphonylmethoxyethyl)adenine and mitoxantrone. The cGMP transporter had a unique pharmacological profile, different from that of MRP1, but with some characteristics in common with MRP4 and MRP5.

Adenosine Triphosphate↗

PubMed2003

Aspirin and stroke prevention.

According to meta-analyses aspirin provides a relative reduction in the rate of major vascular events of 19% in patients with arterial disease in general, whereas for patients with ischaemic cerebrovascular disease this reduction is only 13%. The discrepancy may well result from pathophysiological differences and not from a play of chance. There is no proven difference in efficacy according to dose. The evidence for this equivalence is most compelling in the range between 75 and 1300 mg daily, but still fairly convincing for doses between 30 and 50 mg. In contrast, side effects are clearly more frequent as the dose is higher. Other antiplatelet agents (sulfinpyrazone, ticlopidine, clopidogrel, dipyridamole, orally administered IIb/IIIa inhibitors) have no clear advantages over aspirin and in some cases definite disadvantages; the combination of aspirin and dipyridamole may be more efficacious than aspirin alone, but the evidence hinges on a single trial. If recurrent TIAs occur under treatment with aspirin, the rational response is not to change to a different antiplatelet agent, but to review the diagnosis and consider causes other than artery-to-artery embolism. Platelet aggregation can probably still occur despite complete acetylation of platelets, via pathways other than COX-1 inhibition, but in vitro aggregation tests are an unreliable measure.

Aspirin↗

PubMed1987

The St. Jude Medical cardiac valve in infants and children: role of anticoagulant therapy.

The experience at the University of Colorado with the St. Jude Medical cardiac valve was reviewed to determine the feasibility of placing this prosthesis in children and the role of anticoagulation. A St. Jude Medical cardiac valve was placed in 33 patients ranging in age from 2.5 months to 17 years. Seven patients were less than 1 year of age. Nineteen valves were placed in the aortic position in patients aged 5 months to 17 years (mean 9.5 years). Five patients had valve replacement only, 13 had concomitant aortoventriculoplasty and 1 a Manouguian procedure. Indications for anulus enlarging procedures were recurrent subaortic stenosis or inability to place an adult-sized valve in the native aortic anulus, or both. There were no early or late deaths. Fourteen valves were placed in the mitral position. They were anular positioned in 6 patients aged 6 months to 16 years and supraanular positioned in 8 patients aged 2.5 months to 2 years. There were no deaths with the anular positioned replacements and seven deaths (two early and five late) with the supraanular positioned replacements. Four of the five late deaths were associated with marked pre- and postoperative left ventricular dysfunction. The follow-up time was 784 patient-months in 31 long-term survivors. Anticoagulation was achieved with warfarin, usually in combination with sulfinpyrazone, dipyridamole or aspirin. There were four episodes of thromboembolism, three occurring in patients with suboptimal anticoagulation, and one in a patient lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2000

Von Willebrand's factor mediates the adherence of human tumoral cells to human endothelial cells and ticlopidine interferes with this effect.

The aim of this study was to explore whether von Willebrand's factor (vWF) plays a role in the adhesion of human colon tumor cells to human endothelial cells in our coculture system. Cell colony density was evaluated basally (endothelial plus colon tumor cells) and following the addition of: purified vWF, vWF plus vWF-blocking antibodies, antibodies against various integrins and adhesion molecules (alpha2 b integrin, beta1 integrin, beta3 integrin, intercellular adhesion molecule-I, intercellular adhesion molecule-II, vitronectin receptor CD61 CD51, laminin alpha6/beta4 receptor), and various drugs inhibiting the hemostatic system (ticlopidine, heparin, acetyl salicylic acid [ASA], defibrotide, indobuphen, dipyridamole, sulfinpyrazone). Furthermore, vWF concentration was measured in the supernatant fluid of the coculture system basally and following the addition of the above-listed drugs. Cell colony density (as measured by light absorption) increased by 33% following the addition of vWF and returned to a value similar to the basal level with antibodies against vWF, while it did not change significantly following the addition of antibodies against the other integrins or adhesion molecules tested. The same parameter was reduced by 35% following the addition of ticlopidine, while it showed a smaller or no change with the other drugs tested. Similarly, vWF concentration in the cell coculture supernatant showed the greatest reduction (from 0.22 to 0.11 mg/mL) following the addition of ticlopidine. These data suggest that vWF mediates the adherence of human tumor cells to human endothelial cells and that ticlopidine interferes with this effect.

Cell Adhesion↗

PubMed2000

A rapid spectrofluorimetric technique for determining drug-serum protein binding suitable for high-throughput screening.

PURPOSE: To develop and validate a rapid method for determining the dissociation constants with which pharmaceutical candidates and drugs bind to serum albumin and to alpha1-acid glycoprotein with the goal of deducing the extent of binding. METHODS: The quenching of the intrinsic tryptophan fluorescence of serum albumin and alpha1-acid glycoprotein was monitored by spectrofluorimetry and the data were used to calculate the apparent dissociation constant. Sodium warfarin was used to probe the warfarin-binding site of serum albumin and diazepam was used to probe the benzodiazepine binding site. Additionally, the binding of sodium salicylate, phenylbutazone, sulfinpyrazone, iophenoxic acid, theophylline, chloramphenicol, acetaminophen, lithium chloride and ampicillin were also investigated. Chlorpromazine hydrochloride and imipramine hydrochloride were used as probes for alpha1-acid glycoprotein. The assays were also extended to the multiwell format. The quenching curves were fitted to the quadratic binding equation to determine the dissociation constants. RESULTS: Intrinsic fluorescence measurements are an excellent predictor of the drug binding to human serum albumin and to alpha1-acid glycoprotein. These measurements detect binding to the warfarin and benzodiazepine binding sites of human serum albumin. The dissociation constants estimated using the method compare favorably to the dissociation constants previously reported by Epps et al. using extrinsic fluorescence methodology, and the results correlate well with equilibrium dialysis using drug displacement endpoints. CONCLUSIONS: These measurements can be carried out with small samples and do not require separation of the bound and unbound species. Additionally, the proposed methods eliminate membrane separations, are not compound specific and do not require analytical chromatography or mass spectrometry for quantitation. Spectrofluorimetry may prove to be a useful method for rapidly determining the protein binding of combinatorial libraries.

Anticoagulants↗

PubMed1980

Acute and latent leukopenic reaction to antipyrine.

During the past 10 yr over 100 subjects received test doses of antipyrine in our laboratory for drug metabolism studies without any noticeable untoward effects. The present case describes an immediate allergic reaction to antipyrine and a latent leukopenic reaction 8 wk later without any drug exposure. Leukoagglutination was demonstrated in vitro following the addition of antipyrine, aminopyrine, phenylbutazone, or sulfinpyrazone to blood taken from the subject.

Adult↗

PubMed2005

Pharmaceutical quality control of acid and neutral drugs based on competitive self-assembly in amphiphilic systems.

An aggregation parameter-based methodology for determining acid and neutral drugs in pharmaceutical dosage forms is presented. The method is based on competitive self-assembly in ternary dye-surfactant-drug aqueous mixtures. Dyes bearing charge of opposite sign to that of surfactants bind to surfactant to form mixed dye-surfactant aggregates, which are monitored from changes in the spectra features of the dye. The drug competes with the dye to interact with the surfactant to form drug-surfactant aggregates, which results in a decrease in the surfactant to dye binding degree proportional to the drug concentration in the aqueous solution. Coomassie Brilliant Blue G (CBBG) and didodecyldimethylammonium bromide (DDABr) were the dye and surfactant reactant used, respectively. The suitability of the surfactant to dye binding degree (SDBD) method to determine drugs with very different molecular structure: propionic (flurbiprofen, ibuprofen, naproxen and ketoprofen) and acetic (diclofenac, felbinac and zomepirac) acids, indolines (indomethacin and sulindac), glycyrrhetinic acid derivatives (carbenoxolone and enoxolone), salicylates (diflunisal and phenyl salicylate), oxicams (meloxicam, piroxicam and tenoxicam), pyrazolones (phenylbutazone and sulfinpyrazone) and hydrocortisones (dexamethasone and prednisolone) has been proved. The proposed method was successfully applied to the determination of drugs in commercial formulates (effervescent granulates, tablets, suppositories, gels and blisters) with a minimum sample treatment (dilution of liquid samples and dissolution of solid samples).

Chemistry, Pharmaceutical↗

PubMed1995

Drugs and surgery in the prevention of ischemic stroke.

Randomized clinical trials have proved that warfarin therapy decreases the risk of stroke in patients with nonvalvular atrial fibrillation and in those who have had a myocardial infarction. In patients who are not candidates for long-term anticoagulant therapy, aspirin is beneficial, but the reduction in risk is smaller with aspirin than with warfarin. In patients with cerebral ischemic symptoms of noncardiac origin, aspirin and ticlopidine reduce the risk of stroke, but the benefit is modest. Given alone, neither dipyridamole nor sulfinpyrazone prevents stroke. The question remains whether either of these drugs plus aspirin is better than aspirin alone. The optimal dose of aspirin for stroke prevention has not been established. Carotid endarterectomy reduces the risk of stroke in symptomatic patients with at least 70 percent stenosis, as determined by arteriography. Current trials are addressing the question of whether endarterectomy is beneficial for patients with moderate degrees of carotid stenosis. The benefit of endarterectomy for patients with asymptomatic carotid lesions remains unclear.

Anticoagulants↗

PubMed1998

ATP-dependent transport of reduced glutathione on YCF1, the yeast orthologue of mammalian multidrug resistance associated proteins.

The transport systems involved in the export of cellular reduced glutathione (GSH) have not been identified, although recent studies implicate a role for some of the multidrug resistance associated proteins (MRP), including MRP1 and MRP2. The present study examined the hypothesis that the yeast orthologue of MRP, Ycf1p, mediates ATP-dependent GSH transport. [3H]GSH transport was measured in vacuolar membrane vesicles isolated from a control strain of Saccharomyces cerevisiae (DTY165), the isogenic DTY167 strain that lacks a functional Ycf1p, and in DTY167 transformed with a 2-micrometer plasmid vector containing YCF1. GSH transport in control vacuolar membrane vesicles was mediated largely by an ATP-dependent, low affinity pathway (Km = 15 +/- 4 mM). ATP-dependent [3H]GSH transport was cis-inhibited by substrates of the yeast Ycf1p transporter and inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, probenecid, and sulfinpyrazone, inhibitors of MRP1 and MRP2, but was minimally affected by membrane potential or pH gradient uncouplers. In contrast, ATP-dependent GSH transport was not seen in vacuolar membrane vesicles isolated from the DTY167 yeast strain without a functional Ycf1p but was restored to near wild-type levels in the DTY167 strain transformed with YCF1 and expressing the vacuolar Ycf1p transporter. On the other hand, expression and functional activity of a bile acid transporter, Bat1p, and of the V-type ATPase were similar in all three yeast strains. These results provide direct evidence for ATP-dependent low affinity transport of GSH by the yeast Ycf1p transporter. Because of the structural and functional homology between Ycf1p and MRP1 and MRP2, these data support the hypothesis that GSH efflux from mammalian cells is mediated by these membrane proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis.

Several points regarding the use of drugs to lower uric acid levels deserve emphasis. First, these agents are not useful in the management of acute gout. Second, all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg/dL. There are no data to support the widely presumed notion that dropping the uric acid level to a very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint function. Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone (Anturane) interact with a number of drugs, and both the patient and physician should be aware of this. Finally, and most important, careful and frequent monitoring is needed during the first several months of therapy with these drugs.

Arthritis, Gouty↗

PubMed1999

A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro.

1. A plasmid containing 1 kb of the CYP3A4 regulatory (promoter) region coupled to a reporter gene for secretary placental alkaline phosphatase (SPAP) was transfected into HepG2 cells. Transfected cells were dosed with several known inducers of CYP3A4 and the levels of SPAP were measured. The effect of co-transfecting a plasmid encoding the human glucocorticoid receptor on reporter gene activity was also examined. 2. Dexamethasone induced CYP3A4-dependent reporter gene expression in a concentration-dependent manner and induction was approximately doubled in the presence of the glucocorticoid receptor. Dexamethasone-dependent induction was blocked by RU-486 (a glucocorticoid receptor antagonist), in the presence of the co-transfected glucocorticoid receptor. 3. Induction of CYP3A4-dependent reporter gene expression and enhancement of the induction by the glucocorticoid receptor was also observed with pregnenolone-16alpha-carbonitrile (PCN), rifampicin, phenytoin, carbamazepine, phenylbutazone and phenobarbitone, all known in vivo inducers of CYP3A4 in man. 4. Metyrapone and sulfinpyrazone induced CYP3A4-dependent reporter gene expression, but induction was not enhanced by the glucocorticoid receptor. 5. Clotrimazole, erythromycin and triacetyloleandomycin (TAO) did not induce CYP3A4-dependent reporter gene expression, consistent with the observation that these inducers act through post-transcriptional mechanisms. 6. These results highlight differences in the molecular mechanisms of induction of CYP3A4 by the xenobiotics studied and indicate that the glucocorticoid receptor is involved in the induction of the CYP3A4 gene by some, but not all, CYP3A4 inducers. 7. We propose that the approach described here provides a useful in vitro approach for the identification of transcriptional regulators of the CYP3A4 gene.

Alkaline Phosphatase↗

PubMed2000

Glucose modulates vitamin C transport in adult human small intestinal brush border membrane vesicles.

The uptake of L-ascorbate (vitamin C) and its oxidized form, dehydro-L-ascorbic acid (DHAA), was evaluated in brush border membrane vesicles isolated from adult human duodenum, jejunum and ileum. Ascorbate was taken up along the entire length of the small intestine with a threefold higher initial uptake rate in distal than proximal segments. Ascorbate uptake was Na(+)-dependent, potential-sensitive and saturable (K(m), 200 micromol/L), whereas DHAA transport involved facilitated diffusion (K(m), 800 micromol/L). Pharmacologic experiments were conducted to characterize further these transport mechanisms. DHAA uptake was not mediated by the fructose carrier GLUT5, the uridine transporter or the 4, 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive anion exchanger of the apical membrane. DIDS and sulfinpyrazone, an inhibitor of the urate/lactate exchanger, both significantly reduced the initial rate of ascorbate uptake. Acidic pH inhibited ascorbate uptake, and this effect was not due to a transmembrane proton gradient. Increasing concentrations of glucose in the transport media also significantly inhibited ascorbate uptake, but no effect of glucose was seen when glucose internalization was blocked by phlorizin. Preloading the vesicles with glucose inhibited ascorbate uptake similarly, indicating that glucose interferes with the ascorbate transporter from the internal side of the membrane. The results of this study suggest that DHAA crosses the apical membrane by facilitated diffusion, whereas ascorbate transport is a Na(+)-dependent, electrogenic process modulated by glucose.

Adult↗

PubMed2002

Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs.

BACKGROUND: Various drug transporters of the ATP-binding cassette (ABC) family restrict the oral bioavailability and cellular, brain, testis, cerebrospinal fluid and fetal penetration of substrate drugs. MDRI P-glycoprotein (P-gp) has been demonstrated to transport most HIV protease inhibitors (HPI) and to reduce their oral bioavailability and lymphocyte, brain, testis and fetal penetration, possibly resulting in major limiting effects on the therapeutic efficacy of these drugs. OBJECTIVES: To investigate whether the ABC transporters MRP1, MRP2, MRP3, MRP5 and breast cancer resistance protein 1 (Bcrp1) are efficient transporters of the HPI saquinavir, ritonavir and indinavir. METHODS: Polarized epithelial non-human (canine) cell lines transduced with human or murine complementary DNA (cDNA) for each of the transporters were used to study transepithelial transport of the HPI. RESULTS: MRP2 efficiently transported saquinavir, ritonavir and indinavir and this transport could be enhanced by probenecid. Sulfinpyrazone was also able to enhance MRP2-mediated saquinavir transport. In contrast, MRP1, MRP3, MRP5, or Bcrp1 did not efficiently transport the HPI tested. CONCLUSIONS: Human MRP2 actively transports several HPI and could, based on its known and assumed tissue distribution, therefore reduce HPI oral bioavailability. It may also limit brain and fetal penetration of these drugs and increase their hepatobiliary, intestinal and renal clearance. MRP2 function and enhancement of its activity could adversely affect the therapeutic efficacy, including the pharmacological sanctuary penetration, of HPI. In vivo inhibition of MRP2 function might, therefore, improve HIV/AIDS therapy.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2005

Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation.

A gas chromatography-mass spectrometry (GC-MS)-based screening procedure was developed for the detection of diuretics, uricosurics, and/or their metabolites in human urine after extractive methylation. Phase-transfer catalyst remaining in the organic phase was removed by solid-phase extraction on a diol phase. The compounds were separated by GC and identified by MS in the full-scan mode. The possible presence of the following drugs and/or their metabolites could be indicated using mass chromatography with the given ions: m/z 267, 352, 353, 355, 386, and 392 for thiazide diuretics bemetizide, bendroflumethiazide, butizide, chlorothiazide, cyclopenthiazide, cyclothiazide, hydrochlorothiazide, metolazone, polythiazide, and for canrenoic acid and spironolactone; m/z 77, 81, 181, 261, 270, 295, 406, and 438 for loop diuretics bumetanide, ethacrynic acid, furosemide, piretanide, torasemide, as well as the uricosurics benzbromarone, probenecid, and sulfinpyrazone; m/z 84, 85, 111, 112, 135, 161, 249, 253, 289, and 363 for the other diuretics acetazolamide, carzenide, chlorthalidone, clopamide, diclofenamide, etozoline, indapamide, mefruside, tienilic acid, and xipamide. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with reference spectra. This method allowed the detection of the abovementioned drugs and/or their metabolites in human urine samples, except torasemide. The limits of detection ranged from 0.001 to 5 mg/L in the full-scan mode. Recoveries of selected diuretics and uricosurics, representing the different chemical classes, ranged from 46% to 99% with coefficients of variation of less than 21%. After ingestion of the lowest therapeutic doses, furosemide was detectable in urine samples for 67 hours, hydrochlorothiazide for 48 hours, and spironolactone for 52 hours (via its target analyte canrenone). The procedure described here is part of a systematic toxicological analysis procedure for acidic drugs and poisons.

Diuretics↗

PubMed2006

Serum urate levels and gout flares: analysis from managed care data.

BACKGROUND: The desired serum urate level (SUA) for prevention of gout attacks is widely recommended to be in the subsaturating range, <6.0 mg/dL. OBJECTIVES: The objectives of this study were to evaluate attainment of this target SUA among gout patients on allopurinol in a naturalistic setting and to assess its impact on gout flare risk. METHODS: : This was a retrospective, observational study in a southeastern U.S. managed care organization of approximately 2.2 million members. The first gout claim/prescription within the intake period (January 1, 2000-December 31, 2002) was the index date. Included patients had > or =2 visits with gout International Classification of Diseases, 9th Revision code (274.xx) or > or =1 pharmacy script(s) for allopurinol, colchicine, probenecid, or sulfinpyrazone. Excluded patients were <18 years and/or did not have a 1-year continuous eligibility pre-/postindex date. Gout flares were defined by office/emergency room visit with gout or joint pain code(s) and > or =1 of the following within 7 days of the visit: intraarticular aspiration/injection, joint fluid microscopy, or pharmacy claim for nonsteroidal antiinflammatory drug, colchicine, corticosteroid, or ACTH. Multivariable regression analyses were conducted to evaluate gout flare risk/rate and association with target SUA. RESULTS: Approximately 40% of 5942 gout patients identified used allopurinol postindex. Among allopurinol users with pre-/postindex SUA data (n = 162), mean SUA was lowered from 8.7 mg/dL to 7.1 mg/dL; reduction was significant (P < 0.001). Among allopurinol users who did not have SUA <6.0 mg/dL preindex (n = 147), only 25% reached target levels during postindex. Despite pharmacotherapy, patients with nontarget levels were 59% more likely to flare than those at target. Allopurinol users who were not at target were 75% more likely to flare. CONCLUSION: The failure of allopurinol users to achieve target SUA levels of <6.0 mg/dL may be attributed to lack of awareness of optimal SUA, allopurinol dosing, compliance, and efficacy. Patients who did not achieve target SUA were at increased flare risk.

Adolescent↗

PubMed1977

Biocompatibility of coated and uncoated charcoal during haemoperfusion in healthy dogs.

The biocompatibility of two commercially available charcoal columns, one containing coated and the other uncoated but immobilized charcoal, was compared during four haemoperfusions with each in eight healthy greyhounds. Reductions in arterial levels of platelets (49% and 42% respectively) and leucocytes (both 21%) were similar. Microaggregates, detected by the Swank screen filtration pressure technique, were found in blood leaving the columns during three of the four perfusions with each column. Another twelve perfusions with the uncoated column were carried out with the addition of one or other of the following three agents which inhibit platelet aggregation: sulfinpyrazone, dipyridamole, or citrate-phosphate-dextrose. With none of these were platelet losses less as compared with the four perfusions in which heparin only was used. However, rises in screen filtration pressure were less pronounced. In other perfusions, where its dosage was varied, heparin was shown to reverse, and in large doses delay, the appearance of micro-aggregates. Thrombus in the column itself may be a source of microaggregates, but platelet aggregation in the absence of thrombus deposition may be responsible. The relation of these findings to micro-aggregate formation, which has constituted a clinical problem during charcoal haemoperfusion in humans with fulminant hepatic failure, is considered.

Animals↗

PubMed1980

HPLC-determination of some antiinflammatory, weak analgesic and uricosuric drugs in human blood plasma and its application to pharmacokinetics.

HPLC-determination of naproxen, indomethacin, ketoprofen, fenoprofen ibuprofen, diclofenac sodium, tolfenamic acid, phenylbutazone, mofebutazone, salicylic acid, acetylsalicylic acid, phenacetin, paracetamol, sulfinpyrazone and probenecid by means of an adjustable, rapid accurate and specific method is described. Plasma samples of 0.2 ml were deproteinised and the drugs extracted simultaneously with pure acetonitrile. Aliquots of 25 mul of this primary extract were directly injected on the column. As elution solvent for drug screening was basically used 55% methanol in 50 mM phosphate buffer at pH 4.0. Optimal separation of some drugs or reasonable elution times for others were obtained by varying the methanol concentration of the elution solvent or possibly its pH. The method used for individual drug determinations is very applicable for therapeutic monitoring purposes as well as for use in pharmacokinetic investigations. As an example, the practical detection limit for naproxen in plasma was about 0.2 microgram ml-1. By concentrating the extract this could be lowered to about 0.04 microgram ml-1. The method was applied in a study of the pharmacokinetics of naproxen in a person, who ingested a single oral dose of 2.5 mg kg-1. Pronounced two-compartment kinetics were found. Vc was 0.038 1 kg-1, Vdss 0.138 1 kg-1, t 1/2 (beta) 21.3 hrs, t 1/2 (alpha) 0.99 hr and t 1/2 (ka) 0.67 hr.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

Evidence of active transport of cadmium complexing dithiocarbamates into renal and hepatic cells in vivo.

A study was made of the effects of certain inhibitors of transport systems on the actions of four cadmium (Cd) complexing N,N-disubstituted dithiocarbamates (DTCs) in mobilizing murine renal and hepatic Cd in vivo. Probenecid, the prototypical antagonist of organic anion transport in the kidney, when given 1 hr prior to each DTC, sharply suppressed the DTC-induced reduction of renal Cd but was virtually without effect on mobilization of Cd from liver. Sulfinpyrazone, which blocks tubular reabsorption of uric acid and also inhibits transport of a variety of organic acids, inhibited markedly the mobilization of both renal and hepatic Cd by DTCs. Phlorizin, an inhibitor of tubular sugar reabsorption, did not affect the Cd mobilizing actions of DTCs in any consistent fashion. We propose that the high degree of selectivity of DTCs in mobilizing renal and hepatic Cd is dependent, at least in part, upon active transport of DTCs into these tissues via the organic anion transport systems. This report presents the first evidence that compounds of the (R)2NCSS- class may gain access to intracellular space by an active, carrier-mediated process.

Animals↗