The effect of verapamil on the nephrotoxic potential of gentamicin as measured by urinary enzyme excretion in healthy volunteers

D. J. Kazierad, G. J. Wojcik, David E. Nix, A. L. Goldfarb, J. J. Schentag

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effects of verapamil on the nephrotoxic potential of multiple-dose gentamicin were studied in healthy adult male volunteers. Subjects received a gentamicin infusion every 8 hours for 19 doses. Gentamicin dosage was adjusted to maintain peak concentrations of 5.5 mg/L and trough concentrations of 0.5 mg/L. Verapamil was given as a sustained release preparation of 180 mg twice daily starting 2 days before the aminoglycoside, and continued for 4 days post-gentamicin therapy. Nephrotoxicity was assessed by measuring 24-hour urinary alanine aminopeptidase excretion (AAP). The urinary AAP results of six subjects given gentamicin with verapamil were compared with urinary AAP from nine subjects treated with gentamicin alone. These nine subjects were matched with the verapamil-treated subjects on the basis of gentamicin area-under-the-curve (AUC). After matching AUC, gentamicin exposure was virtually identical between the two groups with an average gentamicin AUC of 26.61 ± 1.49 and 27.51 ± 1.25 mg · hr/L for the gentamicin/verapamil and gentamicin only groups respectively. Verapamil retarded the rise in mean daily AAP excretion on days 1 to 6 of gentamicin therapy, with a significant difference with respect to AAP urinary excretion (P < .05) observed on day 2. There was no significant difference in total cumulative AAP excretion or in the time to return to baseline AAP excretion. Therefore, verapamil was effective in reducing AAP excretion associated with gentamicin therapy.

Original languageEnglish (US)
Pages (from-to)196-201
Number of pages6
JournalJournal of Clinical Pharmacology
Volume35
Issue number2
StatePublished - 1995
Externally publishedYes

Fingerprint

Verapamil
Gentamicins
Healthy Volunteers
CD13 Antigens
Enzymes
Area Under Curve
Delayed-Action Preparations
Aminoglycosides
Volunteers
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

The effect of verapamil on the nephrotoxic potential of gentamicin as measured by urinary enzyme excretion in healthy volunteers. / Kazierad, D. J.; Wojcik, G. J.; Nix, David E.; Goldfarb, A. L.; Schentag, J. J.

In: Journal of Clinical Pharmacology, Vol. 35, No. 2, 1995, p. 196-201.

Research output: Contribution to journalArticle

@article{3c64cf5553044f0a988aebc1b48dd3ac,
title = "The effect of verapamil on the nephrotoxic potential of gentamicin as measured by urinary enzyme excretion in healthy volunteers",
abstract = "The effects of verapamil on the nephrotoxic potential of multiple-dose gentamicin were studied in healthy adult male volunteers. Subjects received a gentamicin infusion every 8 hours for 19 doses. Gentamicin dosage was adjusted to maintain peak concentrations of 5.5 mg/L and trough concentrations of 0.5 mg/L. Verapamil was given as a sustained release preparation of 180 mg twice daily starting 2 days before the aminoglycoside, and continued for 4 days post-gentamicin therapy. Nephrotoxicity was assessed by measuring 24-hour urinary alanine aminopeptidase excretion (AAP). The urinary AAP results of six subjects given gentamicin with verapamil were compared with urinary AAP from nine subjects treated with gentamicin alone. These nine subjects were matched with the verapamil-treated subjects on the basis of gentamicin area-under-the-curve (AUC). After matching AUC, gentamicin exposure was virtually identical between the two groups with an average gentamicin AUC of 26.61 ± 1.49 and 27.51 ± 1.25 mg · hr/L for the gentamicin/verapamil and gentamicin only groups respectively. Verapamil retarded the rise in mean daily AAP excretion on days 1 to 6 of gentamicin therapy, with a significant difference with respect to AAP urinary excretion (P < .05) observed on day 2. There was no significant difference in total cumulative AAP excretion or in the time to return to baseline AAP excretion. Therefore, verapamil was effective in reducing AAP excretion associated with gentamicin therapy.",
author = "Kazierad, {D. J.} and Wojcik, {G. J.} and Nix, {David E.} and Goldfarb, {A. L.} and Schentag, {J. J.}",
year = "1995",
language = "English (US)",
volume = "35",
pages = "196--201",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "SAGE Publications Inc.",
number = "2",

}

TY - JOUR

T1 - The effect of verapamil on the nephrotoxic potential of gentamicin as measured by urinary enzyme excretion in healthy volunteers

AU - Kazierad, D. J.

AU - Wojcik, G. J.

AU - Nix, David E.

AU - Goldfarb, A. L.

AU - Schentag, J. J.

PY - 1995

Y1 - 1995

N2 - The effects of verapamil on the nephrotoxic potential of multiple-dose gentamicin were studied in healthy adult male volunteers. Subjects received a gentamicin infusion every 8 hours for 19 doses. Gentamicin dosage was adjusted to maintain peak concentrations of 5.5 mg/L and trough concentrations of 0.5 mg/L. Verapamil was given as a sustained release preparation of 180 mg twice daily starting 2 days before the aminoglycoside, and continued for 4 days post-gentamicin therapy. Nephrotoxicity was assessed by measuring 24-hour urinary alanine aminopeptidase excretion (AAP). The urinary AAP results of six subjects given gentamicin with verapamil were compared with urinary AAP from nine subjects treated with gentamicin alone. These nine subjects were matched with the verapamil-treated subjects on the basis of gentamicin area-under-the-curve (AUC). After matching AUC, gentamicin exposure was virtually identical between the two groups with an average gentamicin AUC of 26.61 ± 1.49 and 27.51 ± 1.25 mg · hr/L for the gentamicin/verapamil and gentamicin only groups respectively. Verapamil retarded the rise in mean daily AAP excretion on days 1 to 6 of gentamicin therapy, with a significant difference with respect to AAP urinary excretion (P < .05) observed on day 2. There was no significant difference in total cumulative AAP excretion or in the time to return to baseline AAP excretion. Therefore, verapamil was effective in reducing AAP excretion associated with gentamicin therapy.

AB - The effects of verapamil on the nephrotoxic potential of multiple-dose gentamicin were studied in healthy adult male volunteers. Subjects received a gentamicin infusion every 8 hours for 19 doses. Gentamicin dosage was adjusted to maintain peak concentrations of 5.5 mg/L and trough concentrations of 0.5 mg/L. Verapamil was given as a sustained release preparation of 180 mg twice daily starting 2 days before the aminoglycoside, and continued for 4 days post-gentamicin therapy. Nephrotoxicity was assessed by measuring 24-hour urinary alanine aminopeptidase excretion (AAP). The urinary AAP results of six subjects given gentamicin with verapamil were compared with urinary AAP from nine subjects treated with gentamicin alone. These nine subjects were matched with the verapamil-treated subjects on the basis of gentamicin area-under-the-curve (AUC). After matching AUC, gentamicin exposure was virtually identical between the two groups with an average gentamicin AUC of 26.61 ± 1.49 and 27.51 ± 1.25 mg · hr/L for the gentamicin/verapamil and gentamicin only groups respectively. Verapamil retarded the rise in mean daily AAP excretion on days 1 to 6 of gentamicin therapy, with a significant difference with respect to AAP urinary excretion (P < .05) observed on day 2. There was no significant difference in total cumulative AAP excretion or in the time to return to baseline AAP excretion. Therefore, verapamil was effective in reducing AAP excretion associated with gentamicin therapy.

UR - http://www.scopus.com/inward/record.url?scp=0028795953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028795953&partnerID=8YFLogxK

M3 - Article

C2 - 7751432

AN - SCOPUS:0028795953

VL - 35

SP - 196

EP - 201

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

SN - 0091-2700

IS - 2

ER -