Determination and properties of acetyl conjugate of N-desisopropylpropranolol, AcNDP

Atsuko Noda, Yoko Ono, Xiuzhong Wu, Keiko Kudo, Narumi Jitsufuchi, Seiji Eto, Hiroshi Noda

Research output: Contribution to journalArticle

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Abstract

1-Acetamino-3-(1-naphthyloxy)-2-propanol (AcNDP) detected in human urine was formed as a metabolite of propranolol (PL) via 1-amino-3-(1-naphthyloxy)-2-propanol (N-desisopropylpropranolol, NDP). The excreted amount of AcNDP was determined by GC-MS using an isotope dilution method. More than 40% of total AcNDP in 24 h urine was detected 10 h after the oral administration of PL to two volunteers, and the total amounts during 24 h urine were at least 1.9–3.9% of the PL dose. As AcNDP is an intermediate metabolite of PL, its urinary amount cannot be determined exactly. Incidentally, AcNDP was chemically stable and was not formed from NDP when acetyl CoA was added to the inactivated hepatocyte system. Thus, the acetylation of NDP, an aliphatic primary amine, was confirmed to be catalyzed by N-acetyltransferase, and interestingly, the acetyl conjugation was inhibited not by sulfamethazine but by p-amino benzoic acid.

Original languageEnglish
Pages (from-to)1454-1455
Number of pages2
JournalBiological and Pharmaceutical Bulletin
Volume18
Issue number10
DOIs
Publication statusPublished - Jan 1 1995

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Propranolol
Urine
Sulfamethazine
Acetyl Coenzyme A
Acetyltransferases
Benzoic Acid
2-Propanol
Acetylation
Isotopes
Amines
Oral Administration
Volunteers
Hepatocytes
N-desisopropylpropranolol

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Determination and properties of acetyl conjugate of N-desisopropylpropranolol, AcNDP. / Noda, Atsuko; Ono, Yoko; Wu, Xiuzhong; Kudo, Keiko; Jitsufuchi, Narumi; Eto, Seiji; Noda, Hiroshi.

In: Biological and Pharmaceutical Bulletin, Vol. 18, No. 10, 01.01.1995, p. 1454-1455.

Research output: Contribution to journalArticle

Noda, A, Ono, Y, Wu, X, Kudo, K, Jitsufuchi, N, Eto, S & Noda, H 1995, 'Determination and properties of acetyl conjugate of N-desisopropylpropranolol, AcNDP', Biological and Pharmaceutical Bulletin, vol. 18, no. 10, pp. 1454-1455. https://doi.org/10.1248/bpb.18.1454
Noda, Atsuko ; Ono, Yoko ; Wu, Xiuzhong ; Kudo, Keiko ; Jitsufuchi, Narumi ; Eto, Seiji ; Noda, Hiroshi. / Determination and properties of acetyl conjugate of N-desisopropylpropranolol, AcNDP. In: Biological and Pharmaceutical Bulletin. 1995 ; Vol. 18, No. 10. pp. 1454-1455.
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N2 - 1-Acetamino-3-(1-naphthyloxy)-2-propanol (AcNDP) detected in human urine was formed as a metabolite of propranolol (PL) via 1-amino-3-(1-naphthyloxy)-2-propanol (N-desisopropylpropranolol, NDP). The excreted amount of AcNDP was determined by GC-MS using an isotope dilution method. More than 40% of total AcNDP in 24 h urine was detected 10 h after the oral administration of PL to two volunteers, and the total amounts during 24 h urine were at least 1.9–3.9% of the PL dose. As AcNDP is an intermediate metabolite of PL, its urinary amount cannot be determined exactly. Incidentally, AcNDP was chemically stable and was not formed from NDP when acetyl CoA was added to the inactivated hepatocyte system. Thus, the acetylation of NDP, an aliphatic primary amine, was confirmed to be catalyzed by N-acetyltransferase, and interestingly, the acetyl conjugation was inhibited not by sulfamethazine but by p-amino benzoic acid.

AB - 1-Acetamino-3-(1-naphthyloxy)-2-propanol (AcNDP) detected in human urine was formed as a metabolite of propranolol (PL) via 1-amino-3-(1-naphthyloxy)-2-propanol (N-desisopropylpropranolol, NDP). The excreted amount of AcNDP was determined by GC-MS using an isotope dilution method. More than 40% of total AcNDP in 24 h urine was detected 10 h after the oral administration of PL to two volunteers, and the total amounts during 24 h urine were at least 1.9–3.9% of the PL dose. As AcNDP is an intermediate metabolite of PL, its urinary amount cannot be determined exactly. Incidentally, AcNDP was chemically stable and was not formed from NDP when acetyl CoA was added to the inactivated hepatocyte system. Thus, the acetylation of NDP, an aliphatic primary amine, was confirmed to be catalyzed by N-acetyltransferase, and interestingly, the acetyl conjugation was inhibited not by sulfamethazine but by p-amino benzoic acid.

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