Long-Acting Sulphonamides and Protein-Binding

Newbould, B. B.; Kilpatrick, R.

doi:10.1016/s0140-6736(60)90784-4

Cited by 74 publications

(18 citation statements)

References 9 publications

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“…Acetyl SDZ excretion expressed as per cent of drug excreted was higher in the under-nourished thereby suggesting a greater acetylation of the drug in this group of individuals. It has been reported that the plasma protein binding of sulfonamides determines the rate of acetylation of these drugs by the liver (Newbould, 1960). The increased acetylation of SDZ seen in under-nourished subjects may thus be a result of poor plasma protein binding of the drug, consequent on a lowered serum albumin concentration.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of sulphadiazine in malnutrition.

Shastri¹,

Krishnaswamy²

1979

Brit J Clinical Pharma

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1. The kinetics of sulphadiazine were studied in well‐nourished and under‐nourished subjects. 2. The metabolic clearance rate of a single dose of sulphadiazine given either orally or intravenously was faster in under‐nourished subjects. 3. The plasma protein binding of the drug was found to be reduced in under‐nourished subjects. 4. Blood concentrations (48 h and 72 h) of sulphadiazine tended to be low in the under‐nourished as compared with well‐nourished subjects after administration of multiple doses of the drug. 5. It is concluded that a revision in the dosage schedule may not be necessary in the treatment of under‐nourished subjects with sulphadiazine, since the blood concentrations were higher than the reporte d minimum to combat infection.

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Section: Discussionmentioning

confidence: 99%

Metabolism of sulphadiazine in malnutrition.

Shastri¹,

Krishnaswamy²

1979

Brit J Clinical Pharma

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“…It has been demonstrated [6,7,8,16] that the chemotherapeutically active part of a sulfonamide is that which is non-metabolized and not bound to proteins. This may possibly be true also for other antibacterial compounds, such as TMP, although no proof as yet is available.…”

Section: Binding To Plasma Proteinsmentioning

confidence: 99%

“…It is also supported by the contents of the 2 drugs in the plasma and in several organs. Table III shows the results of experiments in rats treated with one oral (6) dose of 100 mg 35S-SMZ or of 20 mg 2-14C-TMP/kg. Thirty minutes after administration the total radioactivity introduced with TMP is accumulated in certain tissues to a greater extent than in the plasma.…”

Section: Concentration Ratios Of Smz To Tmp In Plasmamentioning

confidence: 99%

Pharmacokinetics of Sulfamethoxazole + Trimethoprim in Man and Their Distribution in the Rat

Schwartz

Rieder²

1970

Chemotherapy

104

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Pharmacokinetic investigations of the combination sulfamethoxazole (SMZ) + trimethoprim (TMP) in adult humans are reported. The subjects received a single oral dose of 800 mg SMZ + 160 mg TMP in the form of 2 tablets Bactrim or 800 mg SMZ + trimethoprim+ 160 mg ¹⁴C-labelled TMP in powder form in gelatine capsules. To investigate the distribution of the drug compo-nents in the body, auxiliary experiments were conducted with rats, using 2––¹⁴C-TMP or ³⁵S-SMZ. The results may be summarized as follows: In the blood plasma of 4 persons given 2 tablets Bactrim peak concentrations of 41.4 to 62.5 μg of non-conjugated SMZ/ml were reached 2 to 4 h after medication and peak levels of 1.27 to 1.86 μg of non-metabolized TMP/ml after 1½ to 4h. The half-life of elimination from plasma, determined in the interval between the 4th and the 24th h after administration, was found to vary for non-metabolized TMP from 4.8 to 11.3 h with a mean of 8.6 h in 10 patients, and for non-acetylated, non-conjugated SMZ from 7.7 to 10.6 h with a mean of 9.0 h in 7 of the mentioned subjects. The fictive volume of distribution varied in four subjects for non-metabolized TMP from 69.0 to 133.3 litres and for non-acetylated non-conjugated SMZ from 10.2 to 16.0 litres. The concentration ratio in the plasma of the non-protein-bound, non-metabolized SMZ, i.e. its therapeutically active part, to that of TMP varied during the first 10 h following medication between 10.4 and 49.2. With regard to the mutual potentiation of the two drugs, these values lie within the optimal range, as has been established for a large spectrum of bacterial species in experiments conducted in vitro and in vivo. The concentrations of the non-acetylated non-conjugated SMZ and of the non-metabolized TMP, i. e. the bacteriostatic fractions of the drugs, in the urine of the first 12 hours after medication were found to vary in 4 healthy adults between 63 and 125 μg/ml and 58 and 158 μg/ml respectively. The corresponding values for the urine of the second 12-hour-period were 27 to 63 μg/ml for SMZ and 19 to 84 μg/mol for TMP. These concentrations ensure good antibacterial effect, the decrease in their ratio (as compared to plasma) being counteracted by the higher content of both drugs in the urine. The average cumulative urinary excretion of total SMZ found in 7 healthy adults and of total TMP determined in 3 persons reached, 12 h after medication (i. e. at the end of the normal dosage interval), 39.6 and 35.9 % of the dose respectively. The corresponding figures after 24 h were 69.2 and 58.6 %, those after 96 h 97.5 and 81.3 % of the dose.

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“…It has, in fact been reported that only 30% of the drug administered is normally excreted in the acetyl form in urine. Newbould & Kilpatrick (1960) have demonstrated that although protein binding determines the rate of glomerular filtration, different sulphonamides are reabsorbed by the renal tubules at different rates, thus masking the effects of protein binding on glomerular filtration.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of sulphafurazole in undernutrition.

Shastri¹

1980

Brit J Clinical Pharma

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1 An oral dose of 75 mg/kg body weight was used to study the kinetics of sulphafurazole in wellnourished and undernourished adult subjects. 2 There were no differences in the half‐life, volume of distribution and total body clearance of the drug in the two groups of subjects. 3 The plasma protein binding of sulphafurazole was significantly reduced in the undernouished subjects. 4 It is concluded that alternations in the dosage schedule may not be necessary in the treatment of undernourished adults with sulphafurazole.

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Long-Acting Sulphonamides and Protein-Binding

Cited by 74 publications

References 9 publications

Metabolism of sulphadiazine in malnutrition.

Metabolism of sulphadiazine in malnutrition.

Pharmacokinetics of Sulfamethoxazole + Trimethoprim in Man and Their Distribution in the Rat

Kinetics of sulphafurazole in undernutrition.

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