Feasibility of interspecies extrapolation in determining the bioequivalence of animal products intended for intramuscular administration

Martinez, Marilyn N.; Pedersoli, W. M.; Ravis, William R.; Jackson, Jean; Cullison, R.

doi:10.1046/j.1365-2885.2001.00316.x

Cited by 14 publications

(21 citation statements)

References 21 publications

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“…injection. The terminal elimination half-lives were estimated to be at least 2.4 h, which was greater than the literature values for sheep and calves (literature value for swine is not available) and it was concluded that this is likely to be associated with flip-flop pharmacokinetics [96]. …”

Section: Drug Examplesmentioning

confidence: 99%

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Yáñez

Remsberg

Sayre

et al. 2011

Therapeutic Delivery

189

108

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Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulation characteristics such as the drug chemical entities themselves or the incorporated excipients can also cause the phenomenon. Yet another contributing factor is the physiological makeup of the extravascular site of administration. In this article, these causes of flip-flop pharmacokinetics are discussed with incorporation of relevant examples and the implications for drug development outlined.

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Section: Drug Examplesmentioning

confidence: 99%

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Yáñez

Remsberg

Sayre

et al. 2011

Therapeutic Delivery

189

108

View full text Add to dashboard Cite

show abstract

“…For example, the comparative bioavailability (expressed as area under the concentration versus time curve, AUC) of two ampicillin formulations (ampicillin trihydrate aqueous versus ampicillin oily suspension) following intramuscular (IM) injections was equivalent in calves but was not equivalent in swine (5). Similarly, comparing two ivermectin formulations in swine versus cattle, Lifschitz et al (6) observed nearly identical time to peak concentrations (Tmax) following subcutaneous (SC) injections of two formulations in cattle, but markedly different Tmax values when these two formulations were administered via SC injection to swine.…”

Section: Differences In Parenteral Drug Absorptionmentioning

confidence: 99%

Factors Influencing the Use and Interpretation of Animal Models in the Development of Parenteral Drug Delivery Systems

Martinez

2011

AAPS J

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Abstract. Depending upon the drug and drug delivery platform, species-specific physiological differences can lead to errors in the interspecies extrapolation of drug performance. This manuscript provides an overview of the species-specific physiological variables that can influence the performance of parenteral dosage forms such as in situ forming delivery systems, nanoparticles, microspheres, liposomes, targeted delivery systems, lipophilic solutions, and aqueous suspensions. Also discussed are those factors that can influence the partitioning of therapeutic compounds into tumors, the central nervous system and the lymphatics. Understanding interspecies differences in the movement and absorption of molecules is important to the interpretation of data generated through the use of animal models when studying parenteral drug delivery.

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“…administration of ampicillin trihydrate at 17.6 mg/kg, was 7.39 ± 0.9 μ g/mL. In comparison, a value (mean ± SD) of 3.18 ± 0.21 μ g/mL has been reported in the literature after 6.6 mg/kg (Martinez et al. , 2001).…”

Section: Discussionmentioning

confidence: 90%

“…injection, which corresponds with a previously reported t max value of 0.5 h after i.m. administration (Martinez et al. , 2001).…”

Section: Discussionmentioning

confidence: 99%

Ampicillin pharmacokinetics in swine following needle‐free, intramuscular, and intravenous administration

Apley

Coetzee

Imerman

et al. 2007

Vet Pharm & Therapeutics

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A cross-over study design was used to determine the pharmacokinetics of ampicillin in swine. Each of eight pigs was subjected to all of the following three treatments: (1) intramuscular (i.m.) injection of 17.6 mg/kg of ampicillin trihydrate; (2) injection of a mean dose of 17.6 mg/kg of ampicillin trihydrate using a needle-free (NF) injection device; and (3) intravenous injection of 17.6 mg/kg of sodium ampicillin administered as a bolus. Ampicillin trihydrate administered by NF injection in this study was not statistically different from i.m. injection as measured by AUC(0-infinity), MRT, MAT, or Cmax. However, the 90% confidence limits about the difference in NF to i.m. mean Cmax and AUC(0-infinity) values, expressed relative to the i.m. treatment mean, exceeded the traditional bioequivalence limits of +/-20%. In part, failure to demonstrate bioequivalence was attributable to small study size and the large within-subject variability associated with this drug. Therefore the power of this study was not sufficient to definitively prove or disprove bioequivalence and additional studies to describe appropriate dosage regimens for ampicillin trihydrate when administered by NF injection to pigs are warranted.

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Feasibility of interspecies extrapolation in determining the bioequivalence of animal products intended for intramuscular administration

Cited by 14 publications

References 21 publications

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Flip-flop Pharmacokinetics – Delivering a Reversal of Disposition: Challenges and Opportunities During Drug Development

Factors Influencing the Use and Interpretation of Animal Models in the Development of Parenteral Drug Delivery Systems

Ampicillin pharmacokinetics in swine following needle‐free, intramuscular, and intravenous administration

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