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Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses
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| Zeitschriftentitel: | Antimicrobial Agents and Chemotherapy |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Antimicrobial Agents and Chemotherapy, 39, 1995, 5, S. 1082-1086 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Richer, M Allard, S Manseau, L Vallée, F Pak, R LeBel, M Richer, M Allard, S Manseau, L Vallée, F Pak, R LeBel, M |
|---|---|
| author |
Richer, M Allard, S Manseau, L Vallée, F Pak, R LeBel, M |
| spellingShingle |
Richer, M Allard, S Manseau, L Vallée, F Pak, R LeBel, M Antimicrobial Agents and Chemotherapy Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses Infectious Diseases Pharmacology (medical) Pharmacology |
| author_sort |
richer, m |
| spelling |
Richer, M Allard, S Manseau, L Vallée, F Pak, R LeBel, M 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.39.5.1082 <jats:p>The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 600 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed by high-pressure liquid chromatography. We observed a nonlinear relationship (P = 0.02) between the dose and the maximum concentration in plasma as well as between the dose and the area under the concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of a limited absorption process. This resulted in a lower AUC value than expected as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-Howell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetration measured by the ratio of the AUC in blister fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir concentrations in blister fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimated that cefdinir at 200 to 400 mg administered twice daily would be adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes. Seven volunteers experienced episodes of light-to-moderate diarrhea. These adverse events occurred irrespective of dose.</jats:p> Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses Antimicrobial Agents and Chemotherapy |
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| title |
Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_unstemmed |
Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_full |
Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_fullStr |
Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_full_unstemmed |
Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_short |
Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_sort |
suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| topic |
Infectious Diseases Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1128/aac.39.5.1082 |
| publishDate |
1995 |
| physical |
1082-1086 |
| description |
<jats:p>The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 600 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed by high-pressure liquid chromatography. We observed a nonlinear relationship (P = 0.02) between the dose and the maximum concentration in plasma as well as between the dose and the area under the concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of a limited absorption process. This resulted in a lower AUC value than expected as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-Howell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetration measured by the ratio of the AUC in blister fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir concentrations in blister fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimated that cefdinir at 200 to 400 mg administered twice daily would be adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes. Seven volunteers experienced episodes of light-to-moderate diarrhea. These adverse events occurred irrespective of dose.</jats:p> |
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| author | Richer, M, Allard, S, Manseau, L, Vallée, F, Pak, R, LeBel, M |
| author_facet | Richer, M, Allard, S, Manseau, L, Vallée, F, Pak, R, LeBel, M, Richer, M, Allard, S, Manseau, L, Vallée, F, Pak, R, LeBel, M |
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| description | <jats:p>The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 600 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed by high-pressure liquid chromatography. We observed a nonlinear relationship (P = 0.02) between the dose and the maximum concentration in plasma as well as between the dose and the area under the concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of a limited absorption process. This resulted in a lower AUC value than expected as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-Howell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetration measured by the ratio of the AUC in blister fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir concentrations in blister fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimated that cefdinir at 200 to 400 mg administered twice daily would be adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes. Seven volunteers experienced episodes of light-to-moderate diarrhea. These adverse events occurred irrespective of dose.</jats:p> |
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| spelling | Richer, M Allard, S Manseau, L Vallée, F Pak, R LeBel, M 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.39.5.1082 <jats:p>The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 600 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed by high-pressure liquid chromatography. We observed a nonlinear relationship (P = 0.02) between the dose and the maximum concentration in plasma as well as between the dose and the area under the concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of a limited absorption process. This resulted in a lower AUC value than expected as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-Howell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetration measured by the ratio of the AUC in blister fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir concentrations in blister fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimated that cefdinir at 200 to 400 mg administered twice daily would be adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes. Seven volunteers experienced episodes of light-to-moderate diarrhea. These adverse events occurred irrespective of dose.</jats:p> Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses Antimicrobial Agents and Chemotherapy |
| spellingShingle | Richer, M, Allard, S, Manseau, L, Vallée, F, Pak, R, LeBel, M, Antimicrobial Agents and Chemotherapy, Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses, Infectious Diseases, Pharmacology (medical), Pharmacology |
| title | Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_full | Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_fullStr | Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_full_unstemmed | Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_short | Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_sort | suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| title_unstemmed | Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses |
| topic | Infectious Diseases, Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1128/aac.39.5.1082 |