Abstract
The mechanism of renal excretion of diprophylline (DPP) and the effect of probenecid on the active transport of DPP in renal tubules were investigated in rats. The concentration of DPP in plasma increased in proportion to the doses of 10, 30, and 60 mg/kg. The pharmacokinetic parameters and the urinary excretion of DPP did not change significantly with the dose. These findings indicate that DPP possesses dose‐independent pharmacokinetics. Pharmacokinetic parameters for tubular secretion of DPP, as determined by a single‐injection renal clearance method, were 21.25 μg/mL for the Michaelis‐Menten constant and 102.38 μg/min for maximum velocity. Coadministration of probenecid decreased the total body clearance of DPP but did not change in the steady‐state volume of distribution of DPP. The effect of probenecid concentration on the steady‐state renal clearance of DPP was evaluated by continuously infusing probenecid at various rates. The renal clearance of DPP decreased as the probenecid concentration increased, a result indicating that probenecid inhibits the tubular secretion of DPP. However, probenecid did not inhibit the renal secretion of DPP completely, probably because of the existence of probenecid‐insensitive transport systems for DPP in the renal proximal tubule. The Michaelis‐Menten constant, maximum velocity, and glomerular filtration rate, as calculated with the competitive inhibition model for renal clearance of DPP, correlated well with estimated values after a single intravenous administration, as described earlier. The competitive inhibition constant of probenecid was 15.86 μg/mL.
| Original language | English |
|---|---|
| Pages (from-to) | 1024-1027 |
| Number of pages | 4 |
| Journal | Journal of Pharmaceutical Sciences |
| Volume | 81 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 01-01-1992 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Pharmaceutical Science
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Pharmacokinetics and the effect of probenecid on the renal excretion mechanism of diprophylline. / Nadai, Masayuki; Apichartpichean, Ruttikorn; Hasegawa, Takaaki; Nabeshima, Toshitaka.
In: Journal of Pharmaceutical Sciences, Vol. 81, No. 10, 01.01.1992, p. 1024-1027.Research output: Contribution to journal › Article
TY - JOUR
T1 - Pharmacokinetics and the effect of probenecid on the renal excretion mechanism of diprophylline
AU - Nadai, Masayuki
AU - Apichartpichean, Ruttikorn
AU - Hasegawa, Takaaki
AU - Nabeshima, Toshitaka
PY - 1992/1/1
Y1 - 1992/1/1
N2 - The mechanism of renal excretion of diprophylline (DPP) and the effect of probenecid on the active transport of DPP in renal tubules were investigated in rats. The concentration of DPP in plasma increased in proportion to the doses of 10, 30, and 60 mg/kg. The pharmacokinetic parameters and the urinary excretion of DPP did not change significantly with the dose. These findings indicate that DPP possesses dose‐independent pharmacokinetics. Pharmacokinetic parameters for tubular secretion of DPP, as determined by a single‐injection renal clearance method, were 21.25 μg/mL for the Michaelis‐Menten constant and 102.38 μg/min for maximum velocity. Coadministration of probenecid decreased the total body clearance of DPP but did not change in the steady‐state volume of distribution of DPP. The effect of probenecid concentration on the steady‐state renal clearance of DPP was evaluated by continuously infusing probenecid at various rates. The renal clearance of DPP decreased as the probenecid concentration increased, a result indicating that probenecid inhibits the tubular secretion of DPP. However, probenecid did not inhibit the renal secretion of DPP completely, probably because of the existence of probenecid‐insensitive transport systems for DPP in the renal proximal tubule. The Michaelis‐Menten constant, maximum velocity, and glomerular filtration rate, as calculated with the competitive inhibition model for renal clearance of DPP, correlated well with estimated values after a single intravenous administration, as described earlier. The competitive inhibition constant of probenecid was 15.86 μg/mL.
AB - The mechanism of renal excretion of diprophylline (DPP) and the effect of probenecid on the active transport of DPP in renal tubules were investigated in rats. The concentration of DPP in plasma increased in proportion to the doses of 10, 30, and 60 mg/kg. The pharmacokinetic parameters and the urinary excretion of DPP did not change significantly with the dose. These findings indicate that DPP possesses dose‐independent pharmacokinetics. Pharmacokinetic parameters for tubular secretion of DPP, as determined by a single‐injection renal clearance method, were 21.25 μg/mL for the Michaelis‐Menten constant and 102.38 μg/min for maximum velocity. Coadministration of probenecid decreased the total body clearance of DPP but did not change in the steady‐state volume of distribution of DPP. The effect of probenecid concentration on the steady‐state renal clearance of DPP was evaluated by continuously infusing probenecid at various rates. The renal clearance of DPP decreased as the probenecid concentration increased, a result indicating that probenecid inhibits the tubular secretion of DPP. However, probenecid did not inhibit the renal secretion of DPP completely, probably because of the existence of probenecid‐insensitive transport systems for DPP in the renal proximal tubule. The Michaelis‐Menten constant, maximum velocity, and glomerular filtration rate, as calculated with the competitive inhibition model for renal clearance of DPP, correlated well with estimated values after a single intravenous administration, as described earlier. The competitive inhibition constant of probenecid was 15.86 μg/mL.
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U2 - 10.1002/jps.2600811014
DO - 10.1002/jps.2600811014
M3 - Article
VL - 81
SP - 1024
EP - 1027
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 10
ER -