Renal tubular transport of nitrofurantoin

Buzard, James A.; Bender, Raymond C.; Nohle, Esther G.; Humphrey, Donald T.; Paul, Mary F.

doi:10.1152/ajplegacy.1962.202.6.1136

Cited by 22 publications

(4 citation statements)

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“…Nitrofurantoin is a weak organic acid with a pKa of 7-2 (Paul & Paul, 1964). Buzard, Bender, Nohle, Humphrey & Paul (1962) established that nitrofurantoin is subjected to both tubular secretion and reabsorption in the dog kidney, with evidence that the renal secretion transport system involved is common to the secretion of other weak acids. In particular, selective inhibition of para-aminohippuric acid secretion occurred after nitrofurantoin dosage (Buzard et al, 1962).…”

Section: Discussionmentioning

confidence: 99%

“…Buzard, Bender, Nohle, Humphrey & Paul (1962) established that nitrofurantoin is subjected to both tubular secretion and reabsorption in the dog kidney, with evidence that the renal secretion transport system involved is common to the secretion of other weak acids. In particular, selective inhibition of para-aminohippuric acid secretion occurred after nitrofurantoin dosage (Buzard et al, 1962). The results presented in this report suggest that nitrofurantoin is transported into dog bile by an active secretory process.…”

Section: Discussionmentioning

confidence: 99%

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Excretion of nitrofurantoin in dog hepatic bile

Conklin

Wagner

1971

British J Pharmacology

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Summary After the intravenous administration of nitrofurantoin sodium to dogs at nitrofurantoin doses of 1·5–24·0 mg/kg, a substantial amount of nitrofurantoin is excreted in bile. The bile to blood drug ratios were about 200. A marked hydrocholeretic effect which correlated directly with the amount of nitrofurantoin administered was also observed. The excretion of nitrofurantoin in bile and the hydrocholeretic effect were linear with the dose of drug over the range 1·5–12·0 mg/kg. Maximum increases in hepatic bile flows were usually from 5–10 ml/0·5 h, while average control bile flow was 1·6 ml ± s.d. 0·6/0·5 hours. The lowest dose at which the hydrocholeretic effect was still detectable was 0·09 mg/kg. Apparent saturation of the biliary excretion system for nitrofurantoin and the hydrocholeretic mechanism occurred after a dose of 24·0 mg/kg. Saturation of the urinary system for nitrofurantoin excretion was noted after a dose of 6·0 mg/kg. Biliary nitrofurantoin recoveries ranged from 16·5% ± s.d. 4·2 to 22·6% ± s.d. 4·7 for the 6 h period after doses of 1·5, 30, and 6·0 mg/kg. Urinary nitrofurantoin recoveries for the same interval ranged from 24·1% ± s.d. 6·6 to 36·2% ± s.d. 8·3. In comparison to values obtained in normal dogs, only about one‐tenth of the drug excretion in bile and about one‐fifth of the hydrocholeretic effect were obtained after intravenous drug administration to dogs with hepatic impairment induced by CCl4.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Excretion of nitrofurantoin in dog hepatic bile

Conklin

Wagner

1971

British J Pharmacology

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“…Nitrofurantoin, a weak acid shown to be secreted by the proximal renal tubule transport system (Buzard, Bender, Nohle, Humphrey & Paul, 1962) was apparently removed from the cerebrospinal fluid at the bulk flow rate. Furaltadone, a weak base not subject to renal tubular secretion (unpublished results), was removed from the cerebrospinal fluid at about the same rate.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Concentrations of Certain Nitrofurans in the Aqueous Humour and Cerebrospinal Fluid of the Dog

Buzard

Conklin

1965

British Journal of Pharmacology and Chemotherapy

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both the aqueous humour and cerebrospinal fluid of the dog have been determined for a series of nitrofuran derivatives. The results show that these two fluids accumulate these drugs similarly, with drug-to-drug differences which may be related to their physical properties. METHODSMongrel dogs of either sex, weighing from 20 to 30 kg, were used. The method of obtaining aqueous humour was similar to that of Krause & Yudkin (1930). Instead of ether and amytal anaesthesia, pentobarbitone sodium was used and no local anaesthetic agent was applied to the eyeball. The sclerocorneal junction in the upper and outer quadrant of the eye was pierced with a 27-gauge, 0.5-in. needle attached to a 2-ml. syringe. Samples of cerebrospinal fluid were taken from the cisterna magna with a 17-gauge, 3.5-in. needle attached to a 50-ml. syringe. Blood was taken by venepuncture with heparinized syringes, and the plasma was removed by immediate centrifugation.The drugs were infused intravenously into a saphenous vein at doses ranging from 4 to 10 mg/kg/hr, and samples of aqueous humour, cerebrospinal fluid and blood were collected at the end of the infusion period. The infusion studies were carried out with solutions of the sodium salts of nitrofurantoin Table 4.All drug solutions were infused at a rate of 1.91 ml./min. All infusions were carried out for at least 1 hr in order to ensure adequate opportunity for transfer. A blood sample was taken before and after obtaining the aqueous humour and cerebrospinal fluid. Not more than 15 min elapsed between samples, and the concentrations of these two samples were within 10% of each other. The plasma concentration reported

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“…Even though nitrofurantoin does not produce effective blood levels after therapeutic doses (7), the assumption that this drug posesses antibacterial activity in kidney tissue could be based on the following observations. (i) Stop-flow data indicate that this agent is reabsorbed in the distal tubule and possibly in the adjacent portion of the proximal tubule (1). (ii) Lymph concentrations of nitrofurantoin draining the medulla are higher than cortical lymph levels, and they are much above the inhibitory concentration of several pathogens of the urinary tract (4).…”

Section: Action Of Nitrofurantoinmentioning

confidence: 99%

Site of Action of Nitrofurantoin in Experimental Urinary Tract Infection

Rocha

Teles

Barros

1969

Applied Microbiology

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The effectiveness of nitrofurantoin in suppressing bacterial growth in the urinary tract was evaluated by using two different experimental models. Pyelonephritis was produced in rats by direct inoculation of 104 Escherichia coil in the medulla of left kidney. Ascending urinary tract infection was induced by inoculation into the urinary bladder of 107 Proteus mirabilis, after a partial cystectomy. Nitrofurantoin was shown to be effective in suppressing bladder bacteriuria, in preventing ascending pyelonephritis, and also in preventing bacterial multiplication in kidney tissue following direct inoculation.

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Renal tubular transport of nitrofurantoin

Cited by 22 publications

References 0 publications

Excretion of nitrofurantoin in dog hepatic bile

Excretion of nitrofurantoin in dog hepatic bile

A Comparison of the Concentrations of Certain Nitrofurans in the Aqueous Humour and Cerebrospinal Fluid of the Dog

Site of Action of Nitrofurantoin in Experimental Urinary Tract Infection

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