Relative Systemic Availability of Sulfapyridine from Commercial Enteric‐Coated and Uncoated Sulfasalazine Tablets

Abstract

The absorption of sulfapyridine after a single 2.0-Gm oral dose of sulfasalazine, the drug of choice in the treatment of inflammatory bowel disease, as commercial uncoated and enteric-coated and uncoated tablets was evaluated in four healthy male adults. The peak plasma concentration of sulfapyridine after the enteric-coated tablets occurred at 20 hours on the average (compared to 14 hours for the uncoated tablets) and was only 50% of that attained from the uncoated tablets (P less than 0.05). The low relative extent of systemic availability of sulfapyridine from the enteric-coated tablets (65.5 +/- 6.3 per cent, mean +/- S.E.) compared to uncoated tablets may be due to absorption rate-dependent presystemic metabolism, since the relative extent of sulfapyridine absorption was 92.7 +/- 6.2 per cent compared to uncoated tablets. These findings suggest that enteric-coated and uncoated tablets of sulfasalazine are not bioequivalent. It remains to be determined whether the clinical efficacy of sulfasalazine from enteric-coated tablets is affected.

Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

“…Although this method is better than the urinary recovery method, the intravenous administration of some drugs has not been determined in humans,141,167–232 sometimes because of the low aqueous solubility of the drugs 201. If the drug undergoes extensive hepatic metabolism, the absorption cannot be accurately evaluated by the ratio of urinary excretion of parent drug; this method will under‐estimate the absorption.…”

“…The names of drug and drug‐like compounds and related data are listed in Table 1 and 2. The absorption data was collected and evaluated from 244 papers 1–5, 8–12, 18–251. The following information concerning human drug absorption was recorded from the literature: absorption data given from the literature;oral bioavailability or absolute bioavailability;percentage of cumulative urinary excretion of unchanged drug and its metabolites following oral and intravenous administration;percentage of metabolites in urine or first‐pass effect following oral and intravenous administration;percentage of unchanged drug in urine following oral and intravenous administration;percentage of excretion of drug in bile following oral and intravenous administration;percentage of cumulative excretion of drug in feces following oral and intravenous administration;total recovery of drug in urine and feces following oral and intravenous administration;single dose level in mg or mg/kg and daily oral dose in mg. …”

ADME Evaluation in Drug Discovery. 7. Prediction of Oral Absorption by Correlation and Classification

“…4 According to the reference, the percentage of cumulative drug and its metabolites in urine following oral administration is about 56∼61%. 23 So the %FA of 12 for sulfasalazine is obviously too low, and 65 or 59 seems more reasonable. Second, some compiled %FA data were based on indirect measurements, such as bioavailability, the excretion in urine and feces following oral administration, and the ratio of cumulative urinary excretion of drug-related material following oral and intravenous administration.…”

“…For example, the %FA value of sulfasalazine is 12 in Palm et al's set, is 65 in Wessel et al's set, and 59 in Zhao et al's set . According to the reference, the percentage of cumulative drug and its metabolites in urine following oral administration is about 56∼61% . So the %FA of 12 for sulfasalazine is obviously too low, and 65 or 59 seems more reasonable.…”

Prediction of Human Intestinal Absorption of Drug Compounds from Molecular Structure

“…The set of 86 drug and drug-like compounds and their experimentally derived %HIA values used in this study were gathered from literature sources. These compounds are listed in Table with their experimental %HIA values and references. ,,,,− …”