Oral bioavailability and pharmacokinetic profile of the amoxicillin-clavulanic acid combination after intravenous and oral administration in Turkeys

ABSTRACT The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against Haemophilus influenzae. A computerized pharmacodynamic simulation was performed, and colony counts and β-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, β-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and β-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of ≤0.12 μg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 μg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (≥3 log10 reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in β-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (P ≤ 0.012) amoxicillin concentrations from 4 h on in simulations with β-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of β-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the ftsI gene or β-lactamase production.

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Nimodipine in the Treatment of Subarachnoid Hemorrhage

DICP ◽

10.1177/106002808902300602 ◽

1989 ◽

Vol 23 (6) ◽

pp. 451-455 ◽

Cited By ~ 5

Author(s):

Sally Usdin Yasuda ◽

Karen J. Tietze

Keyword(s):

Subarachnoid Hemorrhage ◽

Adverse Effects ◽

Oral Administration ◽

Calcium Channel Antagonist ◽

Clinical Studies ◽

Oral Bioavailability ◽

Half Life ◽

Cerebral Blood Vessels ◽

Vasodilatory Effect ◽

Intravenous And Oral Administration

Nimodipine, a calcium-channel antagonist with a relatively selective vasodilatory effect on cerebral blood vessels, has recently been approved for improvement of neurologic deficits due to spasm following subarachnoid hemorrhage. Nimodipine has low oral bioavailability (2.7–27.9 percent), a short half-life (2 h), is highly protein bound (98–99 percent), and is hepatically metabolized. Clinical studies have evaluated topical, intravenous, and oral administration of nimodipine for the treatment of cerebral artery spasm associated with subarachnoid hemorrhage. These studies document some benefit of the drug in reducing the occurrence of severe neurologic deficit, although this effect is not universal. Few adverse effects have been noted. Further studies are necessary to evaluate the pharmacologic and pharmacokinetic characteristics, the appropriate dose and route of administration, adverse effects, drug interactions, and the therapeutic efficacy of nimodipine before routine use can be recommended.

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Relative Oral Bioavailability of Two Amoxicillin–Clavulanic Acid Formulations in Healthy Dogs: A Pilot Study

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-6872 ◽

2019 ◽

Vol 55 (1) ◽

pp. 14-22 ◽

Cited By ~ 3

Author(s):

Jennifer Moczarnik ◽

Darren J. Berger ◽

James O. Noxon ◽

Dana N. LeVine ◽

Zhoumeng Lin ◽

...

Keyword(s):

Pilot Study ◽

Clavulanic Acid ◽

Coefficient Of Variation ◽

Oral Bioavailability ◽

Drug Exposure ◽

Comparative Investigation ◽

Pharmacokinetic Parameters ◽

Pilot Investigation ◽

Amoxicillin Clavulanic Acid ◽

Healthy Dogs

ABSTRACT The use of human generic amoxicillin–clavulanic acid formulations in veterinary medicine is currently lacking supportive evidence. This pilot study was conducted to determine preliminary pharmacokinetic parameters and relative oral bioavailability of a human generic and veterinary proprietary 4:1 amoxicillin–clavulanic acid formulation in healthy dogs to evaluate whether drug exposure was similar and to determine if further comparative investigation is warranted. Each dog received a single oral dose of each formulation containing 500:125 mg of amoxicillin–clavulanic acid at two separate instances with a 2 wk washout period between product administration. Following drug administration, blood was collected at fixed times over 24 hr to measure plasma amoxicillin and clavulanic acid concentrations using liquid chromatography–mass spectrometry. There were no statistically significant differences between pharmacokinetic parameters of either formulation. Clavulanic acid showed greater between-dog variation in drug exposure between formulations compared with amoxicillin and was also observed to be more variable within the veterinary proprietary formulation. The average relative oral bioavailability was 98.2% (23.6% coefficient of variation) for amoxicillin and 152.6% (64.3% coefficient of variation) for clavulanic acid between formulations. This pilot investigation supports the need for further bioequivalence studies regarding these formulations before commenting on product interchangeability.

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Pharmacokinetic Evaluation of 3′-Azido-2′, 3′-Dideoxyuridine-5′-O-Valinate-Hydrochloride as a Prodrug of the Anti-HIV Nucleoside 3′-Azido-2′, 3′-Dideoxyuridine

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020301400505 ◽

2003 ◽

Vol 14 (5) ◽

pp. 263-270

Author(s):

Linghui Kong ◽

John S Cooperwood ◽

Shu-Hui Christine Huang ◽

Chung K Chu ◽

F Douglas Boudinot

Keyword(s):

Oral Administration ◽

Intravenous Administration ◽

Oral Bioavailability ◽

Half Life ◽

Dose Range ◽

Parent Compound ◽

Terminal Phase ◽

Pharmacokinetic Parameters ◽

Intravenous And Oral Administration ◽

Anti Hiv

3′-Azido-2′, 3′-dideoxyuridine (AZDU, AzddU, CS-87) has been shown to have potent anti-HIV activity in vitro. However, the compound exhibits a relatively short half-life and incomplete oral bioavailability in humans. In an effort to improve the pharmacokinetic properties of AZDU, prodrug 3′-azido-2′,3′-dideoxyuridine-5′- O-valinate hydrochloride (AZDU-VAL) was synthesized by the esterification of 5′-OH function in AZDU. The objective of this study was to investigate the biotransformation and pharmacokinetics of AZDU-VAL along with its antiviral parent compound AZDU following intravenous and oral administration to rats. Adult male Sprague-Dawley rats were administered AZDU or AZDU-VAL by intravenous injection or oral gavage. Concentrations of AZDU-VAL and AZDU were determined by HPLC. Pharmacokinetic parameters were generated by area-moment analysis. The bioavailability of AZDU after oral administration was approximately 53%. The terminal phase half-life of the nucleoside analogue ranged between 0.6 h after intravenous administration and 1 h following oral administration. In vivo the prodrug was rapidly and efficiently biotransformed to yield AZDU following intravenous and oral administration. The apparent availability of AZDU was virtually complete following oral administration of prodrug AZDU-VAL averaging 101%. The bioavailability of AZDU following intravenous administration of AZDU-VAL averaged 106%. In summary, the disposition of AZDU was dose dependent over the dose range of 25–100 mg/kg. Renal clearance and steady state volume of distribution were lower at the higher dose level. Prodrug AZDU-VAL demonstrated improved oral bioavailability as evidenced by complete absorption and efficient bioconversion to AZDU. The results suggest that AZDU-VAL may be a promising prodrug for the delivery of AZDU.

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Discrepancies in drug labeling texts as a cause of medication errors

Vestnik Roszdravnadzora ◽

10.35576/article_5d135f4a5a9f62.45142755 ◽

2019 ◽

Vol 2019 (3) ◽

pp. 59-62

Author(s):

Анна Кузьмина ◽

Anna Kuz'mina ◽

Ирина Асецкая ◽

Irina Aseckaya ◽

Виталий Поливанов ◽

...

Keyword(s):

Oral Administration ◽

Clavulanic Acid ◽

Medication Errors ◽

Active Substance ◽

Medicinal Products ◽

Suspected Drug ◽

Drug Labeling ◽

Spontaneous Reports ◽

Amoxicillin Clavulanate ◽

Amoxicillin Clavulanic Acid

Contradictions in drug labeling texts for various medicinal products with the same active substance can cause medication errors. We found discrepancies in the Russian drug labeling texts for cefotaxime and oral forms of amoxicillin/clavulanic acid, 500 + 125 mg. We analyzed Russian database of spontaneous reports. In 18.5% spontaneous reports with cefotaxime as a suspected drug and in 22.0% spontaneous reports with amoxicillin/clavulanate in forms for oral administration as a suspected drug we detected medication errors resulted from deviations from those items of approved drug labels which were not harmonized for different drug manufacturers. Such problems require the participation of regulatory authorities in order to eliminate existing discrepancies.

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