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PubMed1997

Probenecid reverses multidrug resistance in multidrug resistance-associated protein-overexpressing HL60/AR and H69/AR cells but not in P-glycoprotein-overexpressing HL60/Tax and P388/ADR cells.

PURPOSE: To determine whether probenecid, an inhibitor of organic anion transport, is able to reverse multidrug resistance (MDR) through modulation of the drug transport function of MDR-associated protein (MRP) and P-glycoprotein (P-gP). METHODS: Two MRP-overexpressing cell lines (HL60/AR and H69/AR) and two P-gP-overexpressing cell lines (HL60/Tax and P388/ADR) were cultured with different concentrations of daunorubicin (DNR) or vincristine (VCR) in the presence or absence of various concentrations of probenecid (0.01-10 mM). Drug sensitivity was determined using an MTT assay. DNR accumulation and subcellular distribution were determined by flow cytometry and confocal microscopy respectively. VCR accumulation was determined by scintillation spectrometry. RESULTS: Probenecid, in a concentration-dependent manner, reversed resistance to DNR and VCR in HL60/AR and H69/AR tumor cell lines. 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. The concentrations of probenecid that reversed MDR are clinically achievable in vivo. In contrast, probenecid did not reverse MDR in either HL60/Tax or P388/ADR tumor cell lines that overexpress P-gP. CONCLUSION: These results suggest that probenecid is an effective chemosensitizer of MRP-associated MDR tumor cells and is a potential candidate for clinical use to reverse MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1985

Inhibitory effects of probenecid on the individual transport routes which mediate the influx and efflux of methotrexate in L1210 cells.

L1210 cells contain a single transport system which mediates the influx of methotrexate and at least three routes for drug efflux [G. B. Henderson and E. M. Zevely, J. biol. Chem. 259, 1526 (1984)]; each of these processes is sensitive to probenecid. The influx carrier was inhibited reversibly and completely by probenecid with a Ki of 0.25 mM, while efflux via the same system was relatively unaffected by this compound (50% inhibition above 2.0 mM). The two remaining efflux routes (which do not contribute to methotrexate influx) showed a much higher sensitivity to probenecid. Efflux via these components was reduced half-maximally at probenecid concentrations of 0.08 and 0.22 mM, respectively, and a complete block was achieved with excess amounts (2.0 mM) of the inhibitor. Intracellular levels of ATP, glucose metabolism, and the membrane potential were also reduced by probenecid, indicating that the mechanism for inhibiting methotrexate efflux may involve the ability of probenecid to act as a metabolic inhibitor. Probenecid may have a broad capacity for inhibiting anion transport processes since it also reduced sulfate influx and efflux via the general anion carrier system.

Animals↗
PubMed1995

Effect of probenecid on the distribution and elimination of ciprofloxacin in humans.

OBJECTIVE: Probenecid-sensitive anion transport systems may be involved in distribution and elimination processes of anionic drugs. The aim of this study was to determine the effect of multiple probenecid treatment on the pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in 12 healthy volunteers. METHODS: A single intravenous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat samples were drawn and analyzed for ciprofloxacin and its 2-aminoethylamino-metabolite (M1) by reversed-phase HPLC. RESULTS: Plasma area under the concentration-time curve and elimination half-life of ciprofloxacin were increased (p < 0.05), and urinary recovery and total and renal clearance decreased (p < 0.05) in the presence of probenecid. Nonrenal clearance and volume of distribution did not differ significantly with and without coadministration of probenecid. Peak plasma concentration, plasma area under the concentration-time curve, and elimination half-life of M1 were increased (p < 0.05) because of the higher amount of M1 formed and the reduced renal clearance (p < 0.05) of the metabolite. Saliva, tear, and sweat exposure were elevated (p < 0.05), but the alterations can be attributed primarily to the different kinetics of ciprofloxacin in plasma. CONCLUSIONS: Coadministration of probenecid altered the renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite kinetics and distribution into saliva, tears, and sweat were affected accordingly, but there was no direct effect of probenecid on these processes. This type of drug-drug interaction might be of clinical relevance when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules.

Adult↗
PubMed1976

Increased rate of disappearance of serum probenecid in barbital dependent rats.

Rats were made barbital dependent by administration of barbital in their drinking water. Subsequently, the rats were either not withdrawn (BN) or withdrawn from barbital for 24 h (BW-24). Before sacrifice, probenecid was administered to measure brain serotonin turnover. A statistically significant decrease in 5-hydroxyindoleacetic acid (5-HIAA) accumulation was observed in the cerebral cortex medulla pons and midbrain. Subsequentialy, serum levels of probenecid were also measured by gas chromatography to determine if chronic barbital consumption might affect circulating probenecid. By ninety minutes following probenecid administration, serum probenecid levels in BN and BW-24 rats were significantly lower than control while a probenecid metabolite was significantly increased. The significantly reduced accumulation of 5-HIAA in brain areas of BN and BW-24 rats is probably the result of the more rapid decline of probenecid rather than a true decrease in serotonin turnover.

Animals↗
PubMed1990

Effects of probenecid on striatal dopamine depletion in acute and long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.

1. The effect of probenecid on striatal dopamine depletion in acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice was examined. 2. Mice treated with a single dose of MPTP (15 mg/kg, s.c.) showed a significant depletion of striatal dopamine throughout a time-course of 7 days. Interestingly, this MPTP-induced striatal dopamine depletion was potentiated by a concomitant injection with a single dose of probenecid (250 mg/kg, i.p.). 3. However, this potentiation of dopamine depletion by probenecid was only a transient phenomenon seen at 4-5 days after the treatment. 4. In a long-term study, mice were treated with the same dosages of MPTP or probenecid plus MPTP twice a week for 5 weeks, we detected that probenecid plus MPTP caused a persistent depletion of striatal DA for 6 months. 5. During this period a partial recovery of DA levels was seen with MPTP alone-treated mice. 6. The detailed mechanisms by which probenecid causes acute potentiation and persistent long-term depletion of striatal dopamine by MPTP are still unclear. 7. With the evidence presented in this study, we determined that after the administration of MPTP in mice, the drug was rapidly metabolized in the periphery and excreted as MPTP N-oxide. 8. Probenecid was shown to inhibit the excretion of urine and urinary MPTP N-oxide shortly after MPTP administration, which may directly or indirectly increase the neurotoxic action of MPTP in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Effect of probenecid on the urinary excretion of TXB2 and PGE2 in the anaesthetised rat.

In the anaesthetised rat, probenecid (33 mg/kg) produced a 50% fall in urinary TXB2 excretion indicating that a component of the TXB2 excreted in the urine is secreted by the proximal tubule. At a higher dose of probenecid (100 mg/kg) this effect was overcome, a relative increase in urinary TXB2 excretion being produced. This may provide evidence for the proximal reabsorption or bi-directional transport of TXB2 in the rat. At 100 mg/kg probenecid also produced an 8-fold increase in urinary PGE2 excretion. Although the bi-directional transport of PGE2 is well known, this is the first time urinary PGE2 excretion rate has been shown to be modified by probenecid. The increase in PGE2 excretion could obscure the assessment of any inhibition by probenecid of proximal PGE2 secretion. It could also provide evidence for the proximal reabsorption of PGE2. However the interpretation of probenecid-induced changes in eicosanoid excretion in terms of modified tubular reabsorption must be treated with caution since urinary eicosanoid excretion could be increased by other properties of probenecid including inhibition of either protein binding or the uptake of eicosanoids into the lung.

Animals↗
PubMed1998

Probenecid hypersensitivity in AIDS: a case report.

BACKGROUND: Cidofovir plus probenecid is a new therapeutic alternative for refractory cytomegalovirus and acyclovir-resistant herpes infections in AIDS patients. Probenecid is used in conjunction with the antiherpetic medication (cidofovir) in order to reduce the incidence of nephrotoxicity by cidofovir. OBJECTIVE: To present therapeutic alternatives for successful administration of probenecid to AIDS patients who develop a hypersensitivity reaction to the medication. METHODS AND RESULTS: We describe a patient with AIDS who was being treated with the cidofovir/probenecid combination for a peri-anal acyclovir-resistant herpetic infection. The patient subsequently developed a cutaneous hypersensitivity reaction to probenecid alone. A pretreatment regimen consisting of prednisone, H1 and H2 blockers was administered before the dosing of probenecid in order for the patient to continue with the antiviral therapy. CONCLUSION: Cutaneous hypersensitivity reactions to probenecid may be seen more frequently with the increasing use of cidofovir in AIDS patients. Our pre-treatment protocol is one therapeutic alternative to be considered in order to continue with probenecid.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Cellular retention of liposome-delivered anionic compounds modulated by a probenecid-sensitive anion transporter.

PURPOSE: Drug carriers such as liposomes may enhance the intracellular delivery of therapeutic agents for infectious or neoplastic diseases. However, the mechanisms affecting cellular retention of liposome contents are understood poorly. We tested the hypothesis that retention of anionic compounds may be modulated by a nonspecific probenecid-sensitive anion transport mechanism, and that liposome composition may determine the impact of such transporters on drug retention by cells. METHODS: The fluorescent anionic dye hydroxy-pyrene-[1,3,6]-trisulfonate (HPTS) was transferred to the cytoplasm of cultured CV-1 or J774 cells by direct needle-microinjection or by ATP-induced permeabilization of the-plasma membrane, respectively, to investigate whether the cells have anion transport mechanisms capable of extruding HPTS from the cytoplasm. Cellular retention of dye was monitored in the presence and absence of the anion transport inhibitors probenecid or sulfinpyrazone. Liposomes containing HPTS were co-labeled with tetramethylrhodamine-labeled phosphatidylethanolamine (Rho-PE) as a marker of liposome membrane fate, and uptake was investigated using J774 cells. RESULTS: Needle-injected HPTS underwent both sequestration in early endocytic vesicles and rapid extrusion into the extracellular medium. Probenecid or sulfinpyrazone reduced the extrusion of HPTS. Thus HPTS is a substrate for a probenecid-sensitive anion transporter in J774 and CV1 cells. After delivery via fluid liposomes composed of phosphatidylglycerol:phosphatidylcholine:cholesterol (3:7:5 mole ratio) and co-labeled with Rho-PE, cell-associated HPTS declined more rapidly than did Rho-PE. Exposure of cells to 5 mM probenecid doubled the quantity of HPTS retained by cells, without changing the retention of the Rho-PE membrane marker. In contrast, the effect of probenecid was negligible when gel-phase liposomes of distearoylphosphatidylglycerol:cholesterol (10:5 mole ratio) were used. CONCLUSIONS: Probenecid-sensitive nonspecific anion transporters can mediate the extrusion of model anions delivered via liposomes. However, liposome composition modulates the amount of material subject to extrusion from cells, possibly by altering the endocytic compartment in which liposomes release their contents.

Animals↗
PubMed2001

Furosemide-probenecid interaction as a laboratory exercise for undergraduate education in clinical pharmacology.

OBJECTIVE: The aim of this study was to determine the easiness, reproducibility, and safety of a laboratory exercise for a drug interaction between furosemide and probenecid. METHODS: From 1995 to 1999 approximately 100 medical students participated in the exercise each year after they gave written informed consent. The students were randomly assigned to one of the three groups in a double-blind fashion: group 1, placebo plus 20 mg of furosemide; group 2, 250 mg of probenecid plus 20 mg of furosemide; and group 3, 1000 mg of probenecid plus 20 mg of furosemide. The students took probenecid or its placebo 1 hour before furosemide. Urine volume and urinary sodium excretion were measured for 3 hours after furosemide. At the end of the exercise in 1999, students responded to several questionnaires concerning the utility of furosemide. RESULTS: The entire course of the exercise was completed within half a day. The following findings were obtained every year. (1) Probenecid dose dependently blunted the diuretic effects of furosemide. (2) Time courses of the diuretic effects were altered by probenecid. Ten to twenty percent of the students had slight complaints but completed the exercise without any medications. Finally, more than 80% of the students considered the exercise to be useful. CONCLUSIONS: The data suggest that the exercise of the drug interaction between furosemide and probenecid is easy to perform, reproducible, and safe. Through the experience of the laboratory exercise, students will develop an attitude to assess and estimate potential drug interactions before they prescribe drugs.

Diuresis↗
PubMed1985

Effect of probenecid on the pharmacokinetics of cefotaxime in sheep.

The effect of probenecid given by intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) injection on the pharmacokinetics of cefotaxime was studied in six Merino ewes. When given intravenously, probenecid increased significantly (P less than 0.05) the plasma half-life of cefotaxime three-fold (to 0.94 +/- 0.32 h) and the area under the curve (AUC) approximately two-fold (to 41.1 +/- 16.8 micrograms.h/ml), and decreased plasma cefotaxime clearance (ClB) 45% (to 0.648 +/- 0.191 l/h/kg). When given with probenecid intravenously, renal clearance (ClR), volume of the central compartment (VC), volume of distribution steady state (Vd(ss], and the amount excreted in urine unchanged did not alter significantly. When given by i.m. injection, probenecid and cefotaxime were well tolerated and cefotaxime was well absorbed (101 +/- 45%). When given by s.c. injection, only 40 +/- 25% cefotaxime was absorbed. When given intramuscularly or subcutaneously, probenecid appeared to reduce the ClB and ClR of cefotaxime, probably because plasma probenecid concentrations are prolonged. Probenecid did not appear to affect the distribution of cefotaxime.

Animals↗
PubMed1985

Pharmacokinetics of probenecid in sheep.

Six Merino ewes were given 1 g (27 g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half-life was 1.55 h and apparent volume of distribution at the steady state (Vdss) 0.18 l/kg. Body clearance (ClB) and renal clearance (ClR) were 0.12 l/h/kg and 0.03 l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 micrograms/ml, respectively, at 15 min; 76, 36, and 34 micrograms/ml at 1 h; and 43, 23 and 34 micrograms/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly. Urine output was correlated positively (P less than 0.05) with kel and ClB. Urine pH increased significantly (P less than 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration.

Animals↗
PubMed1983

Effect of probenecid on the pharmacokinetics of cefmenoxime.

In this study, we were concerned with the effect of probenecid on the pharmacokinetics of 1,000 mg of cefmenoxime administered over a 30-min period by intravenous infusion. Each of a total of 10 subjects received cefmenoxime twice, once with and once without adjunctive probenecid. The data were fit by iterative nonlinear regression procedures to a two-compartment open pharmacokinetic model, with elimination from the central compartment. The mean calculated peak concentration, area under the curve from zero to infinity, and half-life without probenecid were 78.1 micrograms/ml, 77.2 micrograms . h/ml, and 1.14 h, respectively. When cefmenoxime was administered with probenecid, these values were 86.7 micrograms/ml, 158.2 micrograms . h/ml, and 1.78 h, respectively. Averages of about 55 and 46% of the administered doses were recovered in urine samples collected at 0 through 24 h for doses administered without and with probenecid, respectively. The mean corrected renal drug clearance was 159 and 66 ml/min without and with probenecid, respectively. Statistical significance (P less than 0.05) was demonstrated for the differences in beta half-life, (K/net), calculated peak concentration, area under the curve from 0 to infinity, and renal clearance, but not for K21, K12, volume of distribution, or alpha-phase distribution rate constant. The results of this study indicate that tubular secretion is the predominant mechanism of clearance for cefmenoxime and that probenecid alters the pharmacokinetics of the compound by competitively inhibiting its tubular secretion without affecting either the rate or the extent of its distribution.

Adult↗
PubMed1984

Azlocillin and cefonicid penetration into bone enhanced by probenecid.

Azlocillin (AZL) and cefonicid (CFD) penetration into rabbit humerus and scapula was evaluated with and without concomitantly administered probenecid. Groups of animals received either 70 mg of AZL intravenously or 20 mg of CFD intramuscularly per kg of body weight; other groups were pretreated with 40 mg of probenecid per kg before the administration of antibiotics. Peak levels of AZL in the sera of animals not receiving probenecid were 76.0 micrograms/ml at 30 min and declined to 7.7 micrograms/ml by 2.0 h. Maximum concentrations in bone were 2.7 micrograms/g in the humerus and 7.1 micrograms/g in the scapula at 1 h. Pretreatment with probenecid significantly elevated levels of AZL in both serum and bone while increasing the half-life in serum from 0.44 to 0.65 h. Maximum drug concentrations in bones of probenecid-pretreated animals were 3.9 and 11.7 micrograms/g in the humerus and scapula, respectively, with detectable levels persisting in bone for up to 4 h. The peak level of CFD alone in serum was 36.7 micrograms/ml at 30 min and declined to 0.86 micrograms/ml at 8 h. Maximum concentrations in bone were 0.66 micrograms/g in the humerus at 1 h and 1.8 micrograms/g in the scapula at 2 h. Pretreatment with probenecid significantly elevated levels of CFD in both serum and bone while increasing the half-life in serum from 1.4 to 2.94 h. Pretreatment with probenecid achieved maximum concentrations of 1.7 and 2.8 micrograms/g in the humerus and scapula, respectively. Detectable levels of CFD persisted in the humerus for up to 4 h and in the scapula for 8 h.

Animals↗
PubMed2003

Chemosensitization of Plasmodium falciparum by probenecid in vitro.

Resistance to drugs can result from changes in drug transport, and this resistance can sometimes be overcome by a second drug that modifies the transport mechanisms of the cell. This strategy has been exploited to partly reverse resistance to chloroquine in Plasmodium falciparum. Studies with human tumor cells have shown that probenecid can reverse resistance to the antifolate methotrexate, but the potential for reversal of antifolate resistance has not been studied in P. falciparum. In the present study we tested the ability of probenecid to reverse antifolate resistance in P. falciparum in vitro. Probenecid, at concentrations that had no effect on parasite viability alone (50 microM), was shown to increase the sensitivity of a highly resistant parasite isolate to the antifolates pyrimethamine, sulfadoxine, chlorcycloguanil, and dapsone by seven-, five-, three-, and threefold, respectively. The equivalent effects against an antifolate-sensitive isolate were activity enhancements of approximately 3-, 6-, 1.2-, and 19-fold, respectively. Probenecid decreased the level of uptake of radiolabeled folic acid, suggesting a transport-based mechanism linked to folate salvage. When probenecid was tested with chloroquine, it chemosensitized the resistant isolate to chloroquine (i.e., enhanced the activity of chloroquine). This enhancement of activity was associated with increased levels of chloroquine accumulation. In conclusion, we have shown that probenecid can chemosensitize malaria parasites to antifolate compounds via a mechanism linked to reduced folate uptake. Notably, this effect is observed in both folate-sensitive and -resistant parasites. In contrast to the activities of antifolate compounds, the effect of probenecid on chloroquine sensitivity was selective for chloroquine-resistant parasites (patent P407595GB [W. P. Thompson & Co., Liverpool, United Kingdom] has been filed to protect this intellectual property).

Animals↗
PubMed1977

Characteristics of accumulation of probenecid by rabbit kidney cortical slices.

Probenecid was accumulated by renal tissue both under aerobic and anaerobic conditions. The aerobic uptake at a low medium concentration of probenecid was enhanced three- or fourfold by acetate, while metabolic inhibitors and organic anions like p-aminohippurate (PAH), phenol red, and other substituted phenolsulphonphthalein (PSP) dyes which undergo secretion had an inhibitory effect. Octanoate and succinate stimulated aerobic probenecid uptake at low medium concentrations, but inhibited transport of the drug at high levels. Studies on renal homogenates showed that the anaerobic uptake of probenecid is due to binding to tissue constituents. Binding characteristics of PSP dyes to phospholipid vesicles and a representative binding protein, human serum albumin, exhibited close similarity to that of binding to renal tissue. Hydrophobic compounds like octanoate and PSP dyes partially inhibited probenecid binding. In contrast, transport of probenecid was almost completely abolished by these substances and PAH at high medium concentrations. On the basis of the results presented in this paper, it is concluded that renal transport of probenecid occurs by the common organic anion transport system.

Acetates↗
PubMed2003

Pharmacokinetics and renal effects of cidofovir with a reduced dose of probenecid in HIV-infected patients with cytomegalovirus retinitis.

To reduce possible nephrotoxicity, intravenous prehydration with normal saline and administration of probenecid must be used with each infusing of the antiviral cidofovir. The recommended standard-dose probenecid (SDP) regimen is 2 g at 3 hours before cidofovir, then 1 g at 2 and 8 hours after cidofovir (total 4 g). A new regimen of reduced-dose probenecid (RDP), 2 g at 1 hour before cidofovir without additional probenecid administrations after infusion (total 2 g), was compared with SDP using a randomized, open-label, parallel design. A single dose of cidofovir (5 mg/kg) was given as a 1-hour infusion after saline prehydration to 24 HIV-infected patients (11 males, 13 females) with cytomegalovirus retinitis and good renal function. Blood was sampled for 48 hours and urine for 24 hours after the start of the cidofovir infusion. Cidofovir pharmacokinetics did not differ significantly between groups. Average key pharmacokinetic parameters (Cmax, tmax, lambda z, AUC0-infinity, Vss, CL, CLR, fe, ER) for RDP differed by less than 17% from SDP and were consistent with previously reported SDP data. Renal function parameters, other safety endpoints, and adverse events were similar between the groups. Therefore, the reduced-dose regimen of probenecid provided renal protection after a single dose of cidofovir and did not alter the pharmacokinetics of cidofovir in patients with moderately good renal function. Although the overall pharmacokinetic results do not show a significant difference in cidofovir exposure with the new probenecid regimen, the main issue of safety of the new dose regimen, both relating to renal toxicity and probenecid-related adverse events, is not adequately addressed in a small study.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effect of probenecid on tetraethyl ammonium (TEA) transport across basolateral membrane of rabbit proximal tubule.

The effect of probenecid on the transport of tetraethylammonium (TEA) was investigated in rabbit reanal cortical slices in an attempt to ascertain the interaction of organic anion with the organic cation transport system in proximal tubule. Probenecid reversibly inhibited TEA uptake by cortical slices in a dose-dependent manner over the concentration range of 1 and 5 mM. The efflux of TEA was not affected by the presence of 3 mM probenecid. Kinetic analysis indicated that probenecid decreased Vmax without a significant change in Km. Probenecid inhibited significantly tissue oxygen consumption at concentrations of 3 and 5 mM. However, probenecid did not significantly reduce TEA uptake in brush border and basolateral membrane vesicles prepared from renal cortex even at higher concentration of 10 mM. These results indicate that probenecid reduces TEA uptake in cortical slices by inhibiting the tissue metabolism rather than by the interaction with the organic cation transporter.

Animals↗
PubMed2000

Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis.

OBJECTIVE: To determine if low dose daily enteric coated aspirin significantly affects the therapeutic actions of probenecid with respect to serum urate levels or urinary urate excretion. METHODS: Patients with gouty arthritis taking a stable dose of probenecid for at least 3 months were enrolled in a prospective crossover study. Twenty-four hour urinary and serum uric acid levels were measured after 14 days in patients crossed over to receive probenecid alone; probenecid and aspirin 325 mg taken concomitantly; and probenecid followed by aspirin 325 mg at 6 hours. RESULTS: Eleven patients completed the crossover study. The addition of aspirin to a stable dose of probenecid had no significant effect upon serum urate levels or 24 h urinary urate excretion (p > 0.05, paired t test). CONCLUSION: Low dose daily enteric coated aspirin does not significantly interfere with the uricosuric effects of probenecid in patients with gouty arthritis.

Aged↗