Interspecies Pharmacokinetic Scaling, Biological Design and Neoteny

Boxenbaum, Harold; D’Souza, Richard

doi:10.1016/b978-0-12-013319-2.50006-1

Cited by 43 publications

(23 citation statements)

References 63 publications

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“…Considerations of the relationship between drug elimination and physiological parameters such as hepatic or renal blood flow reasonably led to the application of allometric scaling in correlating pharmacokinetics in humans and animal species (Boxenbaum, 1980;Ings, 1990;Ritschel, 1992). Accurate predictions of pharmacokinetics in human by allometric scaling were demonstrated for renally excreted antibiotics (Sawada et al, 1984;Mordenti, 1986) and proteins (Mordenti et al, 1991) as well as for a number of drugs displaying high hepatic extraction (Boxenbaum and D'Souza, 1990). However, for compounds characterized by low and intermediate hepatic extraction, elimination strongly depends on biochemical parameters such as intrinsic clearance and protein binding, which often are highly species specific.…”

mentioning

confidence: 99%

Comparison of Prediction Methods for in Vivo Clearance of (S,s)-3-[3-(Methylsulfonyl)phenyl]-1-Propylpiperidine Hydrochloride, a Dopamine D2 Receptor Antagonist, in Humans

Yamazaki

Toth²,

Black³

et al. 2004

Drug Metabolism and Disposition

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mentioning

confidence: 99%

Comparison of Prediction Methods for in Vivo Clearance of (S,s)-3-[3-(Methylsulfonyl)phenyl]-1-Propylpiperidine Hydrochloride, a Dopamine D2 Receptor Antagonist, in Humans

Yamazaki

Toth²,

Black³

et al. 2004

Drug Metabolism and Disposition

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“…a total of about 3000 million heartbeats per lifetime). This is considered to be a reflection of neoteny (Gould, 1979;Yates and Kugler, 1986;Boxenbaum and D'Souza, 1990), which is the phenomenon of prolonged early development, This approach of finding physiological invariants or constants, is one of the methods that have been exploited in the theoretical analysis of allometric relationships. It is based on an engineering method of analysis called ~ analysis' which is frequently used in scaling up from bench scale models to pilot scale and commercial scale.…”

Section: Allometric Methodsmentioning

confidence: 99%

“…The scaling of these parameters to humans is accomplished by simply substituting the appropriate human value for the body mass (M) into the allometric equations. a Adapted from Kleiber (1947) For chemicals that involve hepatic clearance, both brain weight and body weight may have to be used to obtain the correct scaling (Boxenbaum and D'Souza, 1990). In these cases the physiological parameters of interest are power functions of both brain weight and body weight.…”

Section: Allometric Pharmacokineticsmentioning

confidence: 99%

Scaling toxicity data across species

Chappell¹

1992

Environ Geochem Health

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The response of various species to doses of chemicals can often give the impression that some (such as cattle in the case of molybdenum) are much more susceptible than others to these chemicals. These impressions usually rely on an underlying assumption that equivalent doses are based on mg of the chemical per kg body weight of the animal. That is, that doses scale as the first power of body weight. This assumption is more often wrong than right. When viewed in a more general way, where the scaling is proportional to a power of the body weight and the exponent determined empirically, it is often found that equivalent doses scale with an exponent in the range of 0.6 to 0.8. As a result, larger animals are indeed more susceptible to toxicity on a mg kg(-1) body weight basis, but this is not because of unique differences in the species, but only because of different body sizes. This method of scaling is called allometry or allometric scaling. An early version of this approach was based on body surface area where the exponent is 2/3. More recently, pharmacokinetics has revealed that the reason for the different response of larger animals is related to the slower metabolic and clearance rates for larger animals which give rise to larger biological half-lives for chemicals in the body and to higher tissue concentrations per given dose.

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“…7 Another technique, the correlation analysis, assumes physiological similarity between a single species and humans. 8 This approach is based on a structure-pharmacokinetic relationship of drug disposition. A linear function is used to describe the relationship between a pharmacokinetic variable in a single laboratory animal species and in humans for an aggregate class of compounds.…”

Section: Introductionmentioning

confidence: 99%

Animal Pharmacokinetics and Interspecies Scaling of Ro 25-6833 and Related (Lactamylvinyl)cephalosporins†

Richter¹,

Heizmann²,

Meyer³

et al. 1998

Journal of Pharmaceutical Sciences

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From a series of six (lactamylvinyl)cephalosporins, candidates for clinical evaluation were selected on the basis of their kinetic profile in animals and predicted pharmacokinetics in man. Exploratory pharmacokinetic studies with Ro 25-6833 and five related cephalosporins were performed following intravenous administration to rats, dogs, and cynomolgus monkeys. All compounds were characterized by a high protein binding in rat, monkey, and human plasma (unbound fraction < or = 5%), whereas in dog plasma, protein binding was markedly lower. Accordingly, for most compounds, clearance was highest in dogs, and lowest in monkeys. Comparison of the renal clearance of unbound drug with creatinine clearance suggests a renal elimination of Ro 25-6833 by glomerular filtration in both rats and dogs (urinary excretion in monkey was not determined due to drug instability in monkey urine). All other compounds showed different renal excretion mechanisms in rats and dogs, thus making the validity of allometric scaling questionable. Unbound clearances in man were predicted by allometric scaling (Ro 25-6833 only) and by a correlation analysis of cephalosporin pharmacokinetics in monkey and man. Limitations of both methods are discussed. When Ro 25-6833 was later studied in man, the predicted pharmacokinetic data in man from both approaches were found to be in good agreement with the observed values.

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Interspecies Pharmacokinetic Scaling, Biological Design and Neoteny

Cited by 43 publications

References 63 publications

Comparison of Prediction Methods for in Vivo Clearance of (S,s)-3-[3-(Methylsulfonyl)phenyl]-1-Propylpiperidine Hydrochloride, a Dopamine D2 Receptor Antagonist, in Humans

Comparison of Prediction Methods for in Vivo Clearance of (S,s)-3-[3-(Methylsulfonyl)phenyl]-1-Propylpiperidine Hydrochloride, a Dopamine D2 Receptor Antagonist, in Humans

Scaling toxicity data across species

Animal Pharmacokinetics and Interspecies Scaling of Ro 25-6833 and Related (Lactamylvinyl)cephalosporins†

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