Pharmacokinetic characteristics of N7‐substituted theophylline derivatives and their interaction with quinolone in rats

Takaaki Hasegawa, Masayuki Nadai, Ruttikorn Apichartpichean, Isao Muraoka, Toshitaka Nabeshima, Kenzo Takagi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model‐independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, ∼ 13‐fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

Original languageEnglish
Pages (from-to)962-965
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume80
Issue number10
DOIs
Publication statusPublished - 01-01-1991
Externally publishedYes

Fingerprint

Quinolones
Dyphylline
Theophylline
Pharmacokinetics
Enoxacin
Pharmaceutical Preparations
Urine
Glomerular Filtration Rate
High Pressure Liquid Chromatography
proxyphylline
Kidney

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Hasegawa, Takaaki ; Nadai, Masayuki ; Apichartpichean, Ruttikorn ; Muraoka, Isao ; Nabeshima, Toshitaka ; Takagi, Kenzo. / Pharmacokinetic characteristics of N7‐substituted theophylline derivatives and their interaction with quinolone in rats. In: Journal of Pharmaceutical Sciences. 1991 ; Vol. 80, No. 10. pp. 962-965.
@article{4da1c7840b2a452880c570f212b03c06,
title = "Pharmacokinetic characteristics of N7‐substituted theophylline derivatives and their interaction with quinolone in rats",
abstract = "Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model‐independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50{\%} of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, ∼ 13‐fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.",
author = "Takaaki Hasegawa and Masayuki Nadai and Ruttikorn Apichartpichean and Isao Muraoka and Toshitaka Nabeshima and Kenzo Takagi",
year = "1991",
month = "1",
day = "1",
doi = "10.1002/jps.2600801012",
language = "English",
volume = "80",
pages = "962--965",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

Pharmacokinetic characteristics of N7‐substituted theophylline derivatives and their interaction with quinolone in rats. / Hasegawa, Takaaki; Nadai, Masayuki; Apichartpichean, Ruttikorn; Muraoka, Isao; Nabeshima, Toshitaka; Takagi, Kenzo.

In: Journal of Pharmaceutical Sciences, Vol. 80, No. 10, 01.01.1991, p. 962-965.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacokinetic characteristics of N7‐substituted theophylline derivatives and their interaction with quinolone in rats

AU - Hasegawa, Takaaki

AU - Nadai, Masayuki

AU - Apichartpichean, Ruttikorn

AU - Muraoka, Isao

AU - Nabeshima, Toshitaka

AU - Takagi, Kenzo

PY - 1991/1/1

Y1 - 1991/1/1

N2 - Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model‐independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, ∼ 13‐fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

AB - Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model‐independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, ∼ 13‐fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

UR - http://www.scopus.com/inward/record.url?scp=0025918223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025918223&partnerID=8YFLogxK

U2 - 10.1002/jps.2600801012

DO - 10.1002/jps.2600801012

M3 - Article

VL - 80

SP - 962

EP - 965

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 10

ER -