Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Probenecid”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,333 records · Page 74Linked to original sources
PubMed1974

Comparison of amoxicillin and ampicillin in single-dose oral treatment of males with gonococcal urethritis.

Amoxicillin in single oral doses of 2.0 g, 2.0 g plus 1.0 g probenecid, or 3.0 g was compared with ampicillin 3.5 g plus 1.0 g probenecid in the treatment of 203 males with uncomplicated acute gonococcal urethritis. Cure rates above 95% were produced by all treatments except the 2.0-g amoxicillin dose, which cured 89% of patients. Of 198 pretreatment gonococcus isolates tested by an agar dilution technique for susceptibility to penicillin G, ampicillin and amoxicillin, over 50% showed relative resistance (MIC > 0.06 mug/ml) to the antibiotics. However, amoxicillin was somewhat more active against isolates showing considerable resistance (MIC >/= 1.0 mug/ml) to penicillin G or ampicillin. Adverse effects of amoxicillin were few: two patients reported transient nausea and six noted short-lived diarrhea. No hypersensitivity reactions were observed.

Administration, Oral↗
PubMed1979

Pharmacokinetics and cardiovascular effects in rabbits of a major hydralazine metabolite, the hydralazine pyruvic-acid hydrazone.

The hydrazone of hydralazine and pyruvic acid (HPH) has been recognized as a quantitatively important metabolite of hydralazine in human plasma. We evaluated the disposition of [14C] HPH after its i.v. administration to normal, anephric and probenecid-pretreated rabbits. Renal clearance of HPH in normal rabbits exceeded the glomerular filtration rate by a factor of 3 to 4 and accounted for 80 to 90% of the total body clearance. Active tubular secretion was established by the effect of probenecid pretreatment to reduce the renal clearance of HPH by 80%. Total body clearance of HPH in anephric rabbits was 10% of that of normal animals, emphasizing the minor importance of metabolic conversion for the overall disposition of HPH. HPH in a maximum dose of 50 mumol/kg i.v. had no hypotensive effect in renal hypertensive rabbits and did not interfere with the subsequent hypotensive response to hydralazine. This HPH dose produced plasma levels at least 50 times in excess of those reported in humans after administration of therapeutic doses of parent hydralazine. HPH is consequently of negligible clinical significance, despite the relatively high plasma concentration of this metabolite which occurs after administration of parent hydralazine.

Animals↗
PubMedDate not supplied

Fatty acid transport and metabolism in the isolated perfused rat kidney.

Transport and metabolism of endogenous fatty acids was studied using an isolated rat kidney preparation. Results tended to confirm the inhibitory effects of probenecid on fatty acid uptake by the kidney but, at the concentration used, probenecid was ineffective in changing the distribution of 14C palmitate within tissue lipids. Alpha-bromopalmitate (alphaBP) (0.4 mM), an inhibitor of fatty acid oxidation, caused an initial enhancement of 14C palmitate uptake, a decrease in esterification into tissue phospholipids and an increase in 14C recovered as free fatty acid in the tissue. This increase had no inhibitory effect on entry of fatty acids. alpha BP had no effect on 14C octanoate uptake and appeared not to affect general metabolism. The results are consistent with the possibility that alphaBP interacts with a renal fatty acid binding protein.

Animals↗
PubMed1983

Drug-induced impairment of pulmonary [3H]prostaglandin E1 removal in vivo.

Pulmonary removal of [3H]prostaglandin (PG)E1 was measured from multiple indicator dilution techniques using [14C]dextran as an intravascular marker in mechanically ventilated anesthetized rabbits. Removal of PGE1 was 87 +/- 1% (n = 23) at the peak of the [14C]dextran outflow curve and decreased in a dose-dependent manner when: 1) indocyanine green (ICG) was coadministered in the injection mixture (n = 18; IC50 = 16 microM); or 2 ICG was administered i.v. to achieve a steady-state level (n = 5; IC50 = 80 microM). Cumulative doses of either furosemide (0.1 mmol/kg b.wt.; n = 5) or probenecid (1.0 mmol/kg; n = 10) administered over 2 hr did not significantly affect the removal of PGE1. However, when 0.5 mumol of ICG was added to the injection, both furosemide and probenecid (0.01 mmol/kg) were associated with greater decreases in the removal of PGE1 than would be expected by the effect of ICG alone (P less than .01). These data show that in vivo measurements of pulmonary removal of [3H]PGE1 are predictably affected by various inhibitors of this transport process previously shown in isolated perfused lungs.

Alprostadil↗
PubMed1984

Parenteral augmentin: pharmacokinetics.

The pharmacokinetics of intravenous Augmentin have been investigated and the data found to fit a two compartment model. In the first study, to a crossover design, a bolus injection of 1.2 g Augmentin was given to 8 healthy volunteers with and without probenecid. It was found that the serum concentrations of amoxycillin were increased in the presence of probenecid, but those of clavulanic acid were unaffected. In a second study a further 8 volunteers received an infusion over 30 min of 2.2 g Augmentin. At the end of the infusion, peak concentrations in excess of 100 micrograms/ml were recorded for amoxycillin and 14 micrograms/ml for clavulanic acid. In both studies the serum and urinary concentrations of amoxycillin and clavulanic acid obtained were well above those considered necessary to achieve a therapeutic effect.

Adult↗
PubMed1984

Carbamazepine decreases catecholamine turnover in the rat brain.

The anticonvulsant carbamazepine (100 mg/kg i.p.) increased the levels of 3-methoxy-4-hydroxyphenylglycol sulfate in the rat brain as well as its accumulation after inhibition of acid transport by probenecid. It did not interfere with 3-methoxy-4-hydroxyphenylglycol sulfation in vivo. However, this was not corroborated by the results of turnover studies. The depletion of brain norepinephrine after inhibition of tyrosine hydroxylase or dopamine (DA) beta-hydroxylase rather tended to be decreased and the accumulation of DA in the rat heart after DA beta-hydroxylase inhibition was diminished. Carbamazepine also reduced the depletion of striatal DA after tyrosine hydroxylase inhibition and the accumulation of striatal dopa after central decarboxylase inhibition, but did not affect the levels of the deaminated DA metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, even after pretreatment with probenecid. Therefore, carbamazepine seems to reduce catecholamine turnover in spite of its enhancing action on the firing of norepinephrine and DA neurons reported in the literature. These apparently paradoxical effects might be explained by an interference with the catecholamine storage mechanism. Two other anticonvulsants, diphenylhydantoin and phenobarbital, in doses approximately equieffective to that of carbamazepine with respect to their anticonvulsant action, showed similar although somewhat weaker effects on DA, but not on norepinephrine turnover. Within the catecholamine hypothesis of affective disorders, the reduction of catecholamine turnover by carbamazepine might explain the reported antimanic and antipsychotic effects in patients.

Animals↗
PubMed1983

Mechanisms of renal excretion of cisdichlorodiamine platinum.

Eighteen diuretic rabbits were given cisdichlorodiamine platinum (CDDP) and the clearance of plasma water platinum was determined with a simultaneous inulin clearance. The rabbits were then given probenecid (50 mg/kg) or choline (50 mg/kg) and the clearance of free platinum was calculated. CDDP has a high clearance, exceeding glomerular filtration rate. The drug appears to be secreted by the anionic transport system in the proximal tubule, as the clearance of free platinum is markedly decreased by the administration of probenecid.

Animals↗
PubMedDate not supplied

Intratubular microinjection study of gentamicin transport in the rat.

The intratubular microinjection technique was used to determine the absorptive flux of radioactive gentamicin the rat. Microinjection into the early tubule and late proximal tubule resulted in recoveries of proximal 66.6 +/- 3.6% and 80.4 +/- 3.4%, respectively. Recoveries after microinjection into the distal convoluted tubule averaged 101.0 +/- 4.3%. The addition of tobramycin, phospholipase A, spermine or probenecid to the microinjection solution inhibited gentamicin absorption. These studies indicate that an absorptive flux of gentamicin is present in the superficial proximal tubule and at a nephron site or sites between the superficial proximal and distal tubules. Gentamicin absorption is mediated by a phospholipid carrier with specificity for polyamines and other aminoglycosides. The presence of probenecid in the perfusion solution inhibited the tubular absorption of gentamicin.

Absorption↗
PubMed1983

Effects of divalent cations and sulfhydryl reagents on the p-aminohippurate (PAH) transporter of renal basal-lateral membranes.

A specific system of transport for p-aminohippurate (PAH) is demonstrated in rabbit renal basal-lateral membrane vesicles. The PAH uptake into an intravesicular space is inhibited by probenecid in concentrations above 0.2 mM. The transport is saturable and is also temperature-dependent with an optimum between 37 and 45 degrees C. Divalent cations are able to enhance the uptake 2- to 3-fold. The stimulatory effect of the divalent cations diminishes in the following order: Mg++ = Mn++, Ba++, Ca++ and Sr++. Maximum stimulation occurs between 2.5 and 5 mM Mg++. The divalent cation stimulatory effect is not the result of changes in the size of the vesicles, in the degree of vesiculation, in the net charge of the membrane or of a transient potential difference across the membrane. Several inhibitors, more inhibitory than probenecid, were found. These are: lithium diiodosalicylate; 4-acetamido-4'-isothiocyano 2,2'-disulfonic acid stilbene; the mercurials, mersalyl acid, p-chloromercuriphenyl sulfonate and Hg++; and 5,5'-dithiobis(nitrobenzoate). Among these, mersalyl acid is the most potent inhibitor for PAH uptake. Its inhibitory effect is probably a combination of its reactivity toward sulfhydryl groups and its anionic character. The results with sulfhydryl reagents indicate that the PAH transport system contains sulfhydryl groups which are essential for the uptake activity. These sulfhydryl groups are probably buried in a hydrophobic region within the lipoprotein matrix of the basal-lateral membrane.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1981

Impaired metabolism of azathioprine in carbon tetrachloride-injured rats.

The metabolism of 6-(1-methyl-4-nitro-5-imidazolyl) thiopurine (azathioprine) in liver-injured rats was studied in vivo by measuring the clearance rate (K) of the drug from the blood, and its excretion in the urine. The K values in probenecid, diethyl maleate and carbon tetrachloride (CC14)-treated rats were much smaller than those in control rats. Probenecid, a known inhibitor of glutathione S-transferase, inhibited the urine excretion of azathioprine, and diethyl maleate produced a prompt depletion of hepatic reduced glutathione (GSH). Reduced levels of both GSH and glutathione S-transferase activity were observed in rats treated with CC14. Pretreatment with GSH, producing a slight and temporal increase of GSH in liver, resulted in no significant change of the K value. These findings, together with the reported kinetic data of the transferase, indicate that the conversion of azathioprine to 6-mercaptopurine (6-MP) in vivo may be catalyzed largely enzymatically by glutathione S-transferase in the liver.

Animals↗
PubMed1981

Effects of exercise performance on drugs used in musculoskeletal disorders.

Non-steroidal analgesic and anti-inflammatory drugs (NSAID) are potent inhibitors of prostaglandin synthesis in vivo at commonly achieved concentrations of these drugs. Prostaglandins of the E-series are released by exercising muscles, and their release is inhibited by indomethacin. The consequences, with respect to exercise performance, are unknown. Drugs used for hyperuricemia and gout such as colchicine, allopurinol, probenecid, and sulphinpyrazone have not been implicated in affecting exercise performance. The uricosuric drugs probenecid and sulphinpyrazone may be contraindicated in individuals who exercise heavily because of the increased danger of precipitating uric acid crystals in the kidney tubules. Muscle relaxants do not cause measurable muscle relaxation following usual oral dosage regimens. They are, however, sedatives and this property could influence exercise performance.

Allopurinol↗
PubMed1981

Cerebrospinal fluid penicillin levels during therapy for latent syphilis.

Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL.

Adolescent↗
PubMed1980

Active transport of methotrexate from cerebrospinal fluid in humans.

The cerebrospinal fluid (CSF) efflux kinetics of methotrexate (MTX) were studied in three patients with indwelling Ommaya reservoirs. A small dose of MTX was injected intraventricularly several hr after the start of a high-dose continuous i.v. infusion of MTX. In all patients, the CSF antifolate concentration returned to the preinjection level before the end of the i.v. infusion. This result indicated that the efflux of MTX from CSF in humans is independent of plasma drug concentrations. Efflux kinetics were further characterized in one patient. Serially obtained CSF samples after intraventricular injections demonstrated a biphasic disappearance curve with alpha- and beta-phase half-disappearance times of 1.7 and 6.6 hr, respectively. Prolongation of the beta-phase half-time was associated with oral acetazolamide medication and with increased intracranial pressure, indicating that inhibition of CSF production slows MTX clearance. CSF MTX concentration, however, declined more rapidly than that of simultaneously administered diethylenetriaminepentaacetic acid, an extracellular marker substance excreted by bulk flow, indicating that bulk flow excretion alone is insufficient to account for MTX efflux from human CSF. Evidence that there is an active transport component was provided by probenecid pretreatment which also prolonged the CSF MTX half-life. These findings suggest that both passive and active mechanisms govern MTX efflux from the CSF in humans and that they can be inhibited by acetazolamide and probenecid, respectively.

Acetazolamide↗
PubMed1980

The efficacy of penicillin regimen in treatment of women with culture positive gonorrhea.

In an attempt to improve treatment of women with noncomplicated gonorrhea, assessment revealed compliance to be a problem. Tests of cure rates were above those expected with oral ampicillin. A third regimen was instituted and compared with procaine penicillin and ampicillin. Three physicians participated, each using only one regimen. All tests of cure were done one week after treatment. Only culture positive cases were evaluated.The third regimen, 4.8 million units of aqueous procaine penicillin G (APPG) plus 1 gm probenecid po, followed the next morning by oral ampicillin, 3.5 gm po, with 1 gm probenecid po, proved to have a better test of cure rate. This provides an alternative in situations of poor patient compliance.

Administration, Oral↗
PubMed1980

Mechanism of renal tubular secretion of norepinephrine in the rabbit.

The present studies examined renal tubular secretory mechanisms for norepinephrine (NE) in the anesthetized rabbit. The application of a saline droplet containing [3H]NE and [14C]inulin to the decapsulated surface of the left kidney was associated with a greater urinary recovery of 3H from that kidney than from the right kidney. The urinary ratio of 3H to 14C was greater than that in the droplet [ratio of urinary 3H/14C to droplet 3H/14C (U/D) = 8.6 +/- 1.2, P < .005], indicating tubular influx of [3H]NE. The urinary recoveries of [14C]inulin from both kidneys were not significantly different from each other. At peak excretion, nonmetabolized [3H]NE represented 74 +/- 8% of the 3H excreted from the left kidney. Probenecid significantly suppressed, but did not abolish, the tubular influx of 3H, but did not significantly alter the fraction of total 3H excreted as nonmetabolized [3H]NE. Cyanine 863 virtually abolished the tubular influx of 3H and significantly reduced the fraction of total 3H excreted as nonmetabolized [3H]NE. Surface application of [3H]-p-aminohippurate or [14C]tetraethylammonium produced U/D ratios which were indicative of tubular influx of the ions. Probenecid abolished the tubular influx of [3H]-p-aminohippurate (P < .001), whereas cyanine 863 significantly reduced the tubular influx of [14C]tetraethylammonium (P < .001). Surface application of [3H]mannitol resulted in no evidence of tubular influx (U/D = 1.2 +/- 0.3, N.S.). The results demonstrate that 1) [3H]NE was secreted by the rabbit renal tubule; 2) passive diffusion probably accounted for little of the tubular influx of [3H]NE; and 3) three-quarters of the secreted [3H]NE was secreted as nonmetabolized NE, most likely via cationic transport.

Animals↗
PubMed1995

Secretion of cyclic GMP by cultured epithelial and fibroblast cell lines in response to nitric oxide.

LLC-PK1 epithelial cells and RFL-6 fibroblasts secreted both cyclic AMP (cAMP) and cyclic GMP (cGMP) when costimulated with forskolin and 3-morpholinosydnonimine (a chemical nitric oxide generator). Intracellular cAMP levels as high as 1100 and 12,000 pmol/10(6) cells were achieved for the two cell types, respectively. These levels were high enough to reach approximately 50% saturation of the cAMP transporter and inhibited transport of cGMP to an equal extent, suggesting that the two cyclic nucleotides compete for a common transport system. The rates of secretion of cGMP and cAMP from LLC-PK1 cells increased in proportion to their rates of synthesis as concentrations of stimulant were varied, but increased only 25% relative to intracellular concentrations in response to inhibition of phosphodiesterases by 3-isobutylmethylxanthine. It is proposed that secretion of cyclic nucleotides is not simply proportional to the total intracellular pool in these cells, but rather is coupled to synthesis. In support of this model, oxyhemoglobin was used to trap nitric oxide and block activity of guanylate cyclase in cells treated with 3-morpholinosydnonimine. As a result, secretion of cGMP ceased within 1 min, whereas intracellular levels decreased slowly over 60 min. Probenecid [p-(dipropylsulfamoyl)benzoic acid] is a nonselective antagonist of anion transport that inhibited secretion of cAMP in both cell types but, unexpectedly, blocked synthesis of cGMP, and this was reflected in direct inhibition of soluble guanylate cyclase in cell lysates. Two heat-stable, high molecular weight factors that confer sensitivity to probenecid were identified, and these factors increased the sensitivity of guanylate cyclase to nitric acid by an order of magnitude.

1-Methyl-3-isobutylxanthine↗
PubMed1995

[Mechanism of renal excretion of T-3761, a novel fluoroquinolone agent, in rabbits].

The mechanism of the renal excretion of T-3761, a novel oral fluoroquinolone agent, was studied by renal clearance, stop-flow techniques and analyzing the pharmacokinetics with and without probenecid in rabbits, and which were compared with those of ofloxacin (OFLX). In rabbits probenecid treatment induced increases in the elimination half-life (2.1 times higher) and area under the serum concentration-time curve (3.1 times), and decreases in elimination rate constant (0.44 times) and total body clearance (0.35 times), while volume of distribution showed no significant change. In the stop-flow pattern, a specific peak of T-3761 was observed. On the other hand, a peak of OFLX was observed at the peak of PAH and a small trough at the trough of sodium. And the renal clearance of T-3761 and OFLX were about 4.9 and 3.3 times higher than the corresponding Clcr, respectively. These results suggested that T-3761 was excreted into urine by both glomerular filtration and renal tubular secretion, and was scarcely reabsorbed at distal tubule. The short elimination half-life of T-3761 might be explained by its great ratio of tubular excretion.

Animals↗
PubMed1975

Comparison of trimethoprim-sulfamethoxazole with penicillin and tetracycline in the treatment of uncomplicated gonorrhea in women.

In a collaborative prospective study 327 women with uncomplicated gonococcal cervicitis or proctitis were randomly assigned to one of four treatment groups: (1) aqueous procaine penicillin G, 4.8 million units IM in one session plus 1.0 g probenecide; (2) tetracycline HCI, 9 g over 4 days; (3) trimethoprim, 80 mg-sulfamethoxazole, 400 mg (TMP-SMX) six tablets once daily for 3 days; (4) TMP-SMX, six tablets wtice on 1 dat at a 6-hour interval. They were re-examined 4 to 8 days and 10 to 15 days after completion of therapy. There was no significant difference between the results of the four regimens in the 4- to 8-day period (P greater than 0.36). However, at the 2-week point the results of TMP-SMX given for 3 days were less effective (P smaller than 0.05) than those obtained by penicillin plus probenecid. There was no significant difference between the results of the other regimens at this latter period.

Administration, Oral↗