Disease relevance of Ethamide

• We conclude that the use of penicillin plus probenecid alone for gonorrhea in heterosexual patients carries an unacceptably high risk of postgonococcal chlamydial morbidity [1].
• Among chlamydia-positive patients, postgonococcal urethritis in men and cervicitis in women occurred more often in patients given penicillin plus probenecid [1].
• Eighty-nine men with gonococcal urethritis were randomly treated with trimethoprim-sulfamethoxazole, four tablets (trimethoprin, 320 mg, and sulfamethoxazole, 1,600 mg) twice daily for two days, or ampicillin, 3.5 g, plus probenecid, 1 g, in a single dose [2].
• Hematuria and eosinophilia developed in two patients being treated for bacterial endocarditis with 20 or 24 gm/day of cephalexin given orally together with probenecid (Benemid) [3].
• In separate studies urea influx was inhibited by hypothermia (decrease from 37 degrees to 28 degrees C), by phloretin (0.1 mM in bath), by cyanide (1 mM), but not by probenecid (0.2 mM) [4].

Psychiatry related information on Ethamide

• Chronic, multiple tics of Gilles de la Tourette's disease. CSF acid monoamine metabolites after probenecid administration [5].
• The half-life in plasma of probenecid given as a single intravenous infusion (40 mg per kilogram of body weight) to patients with either Huntington's chorea or Parkinson's disease averaged about 6.6 hours [6].
• Psychomotor performance was decreased in the adinazolam plus probenecid treatment compared with the adinazolam treatment [7].
• The effect of probenecid on spontaneous motor activity in rats [8].
• The probenecid technique was used in study of the central dopamine DA metabolism in patients with depressions, psychotic disorders, and Parkinson's disease [9].

High impact information on Ethamide

• To monitor the efficacy of the 1972 United States Public Health Service recommended treatment regimens for uncomplicated gonorrhea, we studied 9008 patients who were randomly assigned either to aqueous procaine penicillin G, 4.8 million units intramuscularly plus 1 g of oral probenecid, or to one of the three other recommended regimens [10].
• Psychiatric patients studied early during treatment with chlorpromazine and thioridazine demonstrated elevated probenecid-induced accumulations of homovanillic acid, a major dopamine metabolite, in cerebrospinal fluid [11].
• Sulfinpyrazone and probenecid, known inhibitors of multispecific organic anion transport, inhibited this basolateral transport, but not the apical transport of daunorubicin mediated by the apically localized human MDR1 P-glycoprotein in MDR1-transfected LLC-PK1 cells [12].
• The folate receptor works in tandem with a probenecid-sensitive carrier in MA104 cells in vitro [13].
• Circular dichroism studies of renal ligandin revealed percent helical structure similar to hepatic ligandin and primary association contrasts were derived for BSP (10-6 M-1) and PAH, probenecid, and penicillin (10-3 M-1) [14].

Chemical compound and disease context of Ethamide

• The effects of probenecid, a known inhibitor of glucuronidation, on the pharmacokinetics of zidovudine were assessed in eight subjects receiving zidovudine as treatment for human immunodeficiency virus infection [15].
• Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis [16].
• Augmentation of the intracellular levels of polyglutamyl derivatives of methotrexate by vincristine and probenecid in Ehrlich ascites tumor cells [17].
• Elevated Cua/Ccr was suppressed by administration of pyrazinamide, a blocker of tubular secretion of uric acid, but was not affected by probenecid; the effects of drugs on Cua/Ccr were similar to those reported in Wilson's disease [18].
• Aminooxyacetic acid and probenecid protected against DCVC toxicity, indicating a role for metabolism by cysteine conjugate beta-lyase and organic anion transport, respectively [19].

Biological context of Ethamide

• Quinine sulphate prevented the probenecid effect but had no effect on zidovudine kinetics when taken without probenecid by four other subjects [15].
• This dye movement was not appreciably delayed by pretreatment of cells with 5 mM probenecid or chilling the monolayer to 5 degrees C, suggesting that dye movement was due to passive permeation through a membrane pore rather than active transport [20].
• Moreover, kinetic analysis of inhibition by probenecid suggests that it is competitive with respect to either OH- or Cl-. These results suggest that anions and the anion transport system may play a role in exocytosis of a polypeptide hormone [21].
• Furthermore, the pHi recovery following NH4Cl exposure was accelerated by isoproterenol in the presence of probenecid, indicating that the Na(+)-HCO3- cotransport and/or the Na(+)-H+ antiport also could be activated.(ABSTRACT TRUNCATED AT 250 WORDS)[22]
• Cell death was specific as it was also present in a human proximal tubular epithelial cell line (HK-2), but not in a human kidney fibroblast cell line, and was prevented by probenecid [23].

Anatomical context of Ethamide

• We found that probenecid also reversibly inhibited sequestration of dye, indicating that sequestration of dye within cytoplasmic vacuoles was also mediated by organic anion transporters [24].
• Central nervous system metabolism in six children and one adult with the syndrome of chronic multiple tics was studied by measuring the accumulation of acid metabolites of dopamine and serotonin (homovanillic acid [HVA] and 5-hydroxyindole-acetic acid [5-HIAA], respectively) in the CSF following probenecid administration [5].
• Disodium 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) and probenecid, which are known to block anion transport in the erythrocyte, also cause a dose-dependent 90%-100% inhibition of release [21].
• Therefore, LTC4 export from cells of bone marrow origin occurs through a probenecid-sensitive membrane carrier shared by other glutathione conjugates and distinct from the LTB4 carrier export system [25].
• When cells preloaded with LTC4 were resuspended in incremental concentrations of the organic acid transport inhibitor, probenecid, there was a dose-dependent decrease in LTC4 release; GS-DNP and probenecid inhibited LTC4 release in a cumulative fashion, whereas neither inhibited the release of LTB4 from preloaded nondifferentiated HL-60 cells [25].

Associations of Ethamide with other chemical compounds

• Lumbar cerebrospinal fluid homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and probenecid were measured in four subgroups of neuropsychiatrically disturbed children and a contrast group of pediatric patients [26].
• However, a strong correlation was observed between the simultaneous activity of MRP1 and Pgp (quantified as the modulation of calcein-AM uptake by cyclosporin A and probenecid) and the LC50 of DNR (r =.77, P <.0001) [27].
• Interaction of probenecid with methotrexate transport and release in the isolated rat hepatocyte in suspension [28].
• Transport activity of monoglutathionylthiotepa could also be inhibited by probenecid and verapamil, inhibitors of organic anion transport, without influencing the biotransformation capacity of the cells [29].
• Cholate uptake under pH gradient conditions was inhibited by furosemide and bumetanide but not by 4, 4'-diisothiocyano-2,2'-disulfonic stilbene (SITS), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (DIDS), or probenecid [30].

Gene context of Ethamide

• We evaluated the activity of these drugs in combination with PSC833, a P-gp inhibitor, and/or probenecid, an MRP1 inhibitor [31].
• Moreover, coadministration of probenecid and other MRP2-stimulating drugs might lead to unforeseen drug-drug interactions by stimulating MRP2 function, potentially leading to suboptimal levels of taxanes and other anticancer drugs in plasma and tumor [32].
• DESIGN AND METHODS: MRD cells were identified using leukemia-associated phenotypes combined with a fluorescent probe assay with substrate/modulator: Syto16/ PSC833 (Pgp), calcein-AM/probenecid (MRP) and BODIPY-prazosin/Ko143 (BCRP); efflux profiles were directly compared with blasts at diagnosis and relapse from the same patient [33].
• This effect of probenecid on MDR was associated with an increased accumulation of DNR and VCR and correction of the altered subcellular distribution of DNR [34].
• The K(i) value of probenecid for hOAT3, but not for hOATP1B3, was significantly lower than the maximum unbound plasma concentration of probenecid at clinical dosages [35].

Analytical, diagnostic and therapeutic context of Ethamide

• However, in patients re-examined three to 14 days after treatment, only the ampicillin-probenecid regimen was significantly less effective than penicillin probenecid (P less than 0.01) [10].
• This was illustrated by 1) overexpression of MRP-1 by Western blotting and 2) the complete reversal of CQ resistance by the MRP-1 transport inhibitors MK571 and probenecid [36].
• PURPOSE: To compare the safety and efficacy of azithromycin, amoxicillin/probenecid, and doxycycline for the treatment of early Lyme disease, to identify risk factors for treatment failure, and to describe the serologic response in treated patients [37].
• METHODS: The transport behaviour of ritonavir, indinavir and amprenavir in the presence and absence of Pgp modulators and probenecid was investigated in an in vitro blood--brain barrier (BBB) co-culture model and in monolayers of LLC-PK1, LLC-PK1:MDR1, LLC-PK1:MRP1 and Caco-2 cells [38].
• Both ventriculocisternal and cerebral subarachnoid perfusions demonstrated relatively high clearances that could not be blocked by probenecid [39].

References