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The dose level of Drug XYZ is 60 mg/m2 (Hint: Use the table found in p.19 for the conversion factors) a. What is the dose in body weight (mg/kg) basis in dogs? b. What is the dose in body weight (mg/kg) basis in rats? c. What is the dose in body weight (mg/kg) basis in monkeys? d. What is the dose in body weight (mg/kg) basis in humans?

The dose level of Drug XYZ is 60 mg/m2 (Hint: Use the table found in p.19 for the conversion factors) a. What is the dose in body weight (mg/kg) basis in dogs? b. What is the dose in body weight (mg/kg) basis in rats? c. What is the dose in body weight (mg/kg) basis in monkeys? d. What is the dose in body weight (mg/kg) basis in humans?

Phlebotomy Essentials
Phlebotomy Essentials
6th Edition
ISBN:9781451194524
Author:Ruth McCall, Cathee M. Tankersley MT(ASCP)
Publisher:Ruth McCall, Cathee M. Tankersley MT(ASCP)
Chapter1: Phlebotomy: Past And Present And The Healthcare Setting
Section: Chapter Questions
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The dose level of Drug XYZ is 60 mg/m2 (Hint: Use the table found in p.19 for the conversion factors)
a. What is the dose in body weight (mg/kg) basis in dogs?
b. What is the dose in body weight (mg/kg) basis in rats?
c. What is the dose in body weight (mg/kg) basis in monkeys?
d. What is the dose in body weight (mg/kg) basis in humans?

Reference:
Guidance for Industry
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers

the picture attached to my question is page 19 on my pdf 

Pharmacologically active dose (PAD): The lowest dose tested in an animal species with the intended pharmacologic activity. Safety factor (SF): A number by which the HED is divided to introduce a margin of safety between the HED and the maximum recommended starting dose. W: Body weight in kg 15 Contains Nonbinding Recommendations ΑPΡENDIX A: Analysis of Allometric Exponent on HED Calculations An analysis was conducted to determine the effect of the allometric exponent on the conversion of an animal dose to the HED. One can derive the following equation (see Appendix C) for converting animal doses to the HED based on body weights and the allometric exponent (b): HED = animal NOAEL x (Wanimal/Whuman) Conventionally, for a mg/m? normalization b would be 0.67, but a number of studies (including the original Freireich data) have shown that MTDS scale best across species when b = 0.75. The Interagency Pharmacokinetics Group has recommended that W.75 be used for interspecies extrapolation of doses in carcinogenicity studies (EPA 1992). There are no data, however, to indicate the optimal method for converting NOAELS to HEDS. Conversion factors were calculated over a range of animal and human weights using (Wanimal/Whuman)-33 (Wanimal/Whuman)" 0.67. The results are shown in Table 2. Using an allometric exponent of 0.75 had a big effect on the conversion factor for the smaller species mice and rats. Nonetheless, mice are not commonly used for toxicology studies to support the first-in-human clinical trials. In addition, there is evidence that the area under the plasma concentration versus time curves in rats and humans correlates reasonably well when doses are normalized to mg/m (Contrera et al. 1995). We conclude that the approach of converting NOAEL doses to an HED based on body surface area correction factors (i.e., b = 0.67) should be maintained for selecting starting doses for initial studies in healthy volunteers since: (1) mg/m² normalization is widely used throughout the toxicology and pharmacokinetic research communities; (2) mg/m² normalization provides a more conservative conversion; (3) there are no data to suggest a superior method for converting NOAELS; and (4) CDER has significant experience in establishing safe starting doses based on mg/m, and it is readily calculated. or 0.25 to assess the effect on starting dose selection of using b = 0.75 instead of b Table 2: Effect of Allometric Exponent on Conversion Factor" Conversion Factors® Ratio of 0.75 to 0.67 Weight Range (kg) Species Standard b = 0.67 b = 0.75 Mouse Rat Rabbit Monkey Dog conversion factor = (Wanimal/Whuman)' ° human weight range used was 50-80 kg (110-176 lb) ' mean conversion factor calculated across entire animal weight range and human weight 0.018-0.033 0.081 0.075 0.141 1.88 0.09-0.40 0.162 0.156 0.245 1.57 1.30 1.27 1.5-3 0.324 0.33 0.43 1.5-4 0.324 0.37 0.47 6.5-13.0 0.541 0.53 0.62 1.17 (1-b) range 16 Contains Nonbinding Recommendations
Transcribed Image Text:Pharmacologically active dose (PAD): The lowest dose tested in an animal species with the intended pharmacologic activity. Safety factor (SF): A number by which the HED is divided to introduce a margin of safety between the HED and the maximum recommended starting dose. W: Body weight in kg 15 Contains Nonbinding Recommendations ΑPΡENDIX A: Analysis of Allometric Exponent on HED Calculations An analysis was conducted to determine the effect of the allometric exponent on the conversion of an animal dose to the HED. One can derive the following equation (see Appendix C) for converting animal doses to the HED based on body weights and the allometric exponent (b): HED = animal NOAEL x (Wanimal/Whuman) Conventionally, for a mg/m? normalization b would be 0.67, but a number of studies (including the original Freireich data) have shown that MTDS scale best across species when b = 0.75. The Interagency Pharmacokinetics Group has recommended that W.75 be used for interspecies extrapolation of doses in carcinogenicity studies (EPA 1992). There are no data, however, to indicate the optimal method for converting NOAELS to HEDS. Conversion factors were calculated over a range of animal and human weights using (Wanimal/Whuman)-33 (Wanimal/Whuman)" 0.67. The results are shown in Table 2. Using an allometric exponent of 0.75 had a big effect on the conversion factor for the smaller species mice and rats. Nonetheless, mice are not commonly used for toxicology studies to support the first-in-human clinical trials. In addition, there is evidence that the area under the plasma concentration versus time curves in rats and humans correlates reasonably well when doses are normalized to mg/m (Contrera et al. 1995). We conclude that the approach of converting NOAEL doses to an HED based on body surface area correction factors (i.e., b = 0.67) should be maintained for selecting starting doses for initial studies in healthy volunteers since: (1) mg/m² normalization is widely used throughout the toxicology and pharmacokinetic research communities; (2) mg/m² normalization provides a more conservative conversion; (3) there are no data to suggest a superior method for converting NOAELS; and (4) CDER has significant experience in establishing safe starting doses based on mg/m, and it is readily calculated. or 0.25 to assess the effect on starting dose selection of using b = 0.75 instead of b Table 2: Effect of Allometric Exponent on Conversion Factor" Conversion Factors® Ratio of 0.75 to 0.67 Weight Range (kg) Species Standard b = 0.67 b = 0.75 Mouse Rat Rabbit Monkey Dog conversion factor = (Wanimal/Whuman)' ° human weight range used was 50-80 kg (110-176 lb) ' mean conversion factor calculated across entire animal weight range and human weight 0.018-0.033 0.081 0.075 0.141 1.88 0.09-0.40 0.162 0.156 0.245 1.57 1.30 1.27 1.5-3 0.324 0.33 0.43 1.5-4 0.324 0.37 0.47 6.5-13.0 0.541 0.53 0.62 1.17 (1-b) range 16 Contains Nonbinding Recommendations
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