340. Note: On Estimating Relative Potency from Quadratic Log-Dose Response Relationships

Biometrics ◽  
1972 ◽  
Vol 28 (3) ◽  
pp. 875 ◽  
Author(s):  
C. Philip Cox
Keyword(s):  
Dose Response ◽  
Relative Potency

ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

1963 ◽  
Vol 42 (2_Suppl) ◽  
pp. S17-S30
Author(s):  
Fred A. Kind ◽  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Active Compound ◽  
Subcutaneous Injection ◽  
Response Curve ◽  
Parent Compound ◽  
Dose Response Curve ◽  
Relative Potency ◽  
Reference Standard ◽  
Highly Active ◽  
Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

A Random-allocation Graded Dose–Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery

2017 ◽  
Vol 127 (6) ◽  
pp. 934-941 ◽  
Author(s):  
Warwick D. Ngan Kee
Keyword(s):  
Blood Pressure ◽  
Spinal Anesthesia ◽  
Cesarean Delivery ◽  
Dose Response ◽  
Relative Potency ◽  
First Episode ◽  
Response Analysis ◽  
Random Allocation ◽  
Dose Response Study ◽  
Different Doses

Abstract Background Norepinephrine has been investigated as a potential alterative to phenylephrine for maintaining blood pressure during spinal anesthesia for cesarean delivery with the advantage of less depression of maternal heart rate and cardiac output. However, the relative potencies of these two vasopressors have not been fully determined in this context. Methods In a random-allocation, graded dose–response study, 180 healthy patients undergoing spinal anesthesia for elective cesarean delivery received a single bolus of norepinephrine in one of six different doses ranging from 4 to 12 µg or phenylephrine in one of six different doses ranging from 60 to 200 µg to treat the first episode of hypotension. The magnitude of response was measured as the percentage of full restoration of systolic blood pressure to the baseline value. Dose–response analysis was performed using nonlinear regression to derive four-parameter logistic dose–response curves, which were compared to determine relative potency. Results Data were analyzed for 180 patients. The estimated ED50 values (dose giving a 50% response) were norepinephrine 10 µg (95% CI, 6 to 17 µg) and phenylephrine 137 µg (95% CI, 79 to 236 µg). The estimated relative potency ratio for the two drugs was 13.1 µg (95% CI, 10.4 to 15.8 µg). Conclusions Comparative dose–response analysis was completed for norepinephrine and phenylephrine given as a bolus to treat the first episode of hypotension in patients undergoing spinal anesthesia for cesarean delivery. The estimated dose equivalent to phenylephrine 100 µg was norepinephrine 8 µg (95% CI, 6 to 10 µg). These results may be useful to inform the design of future comparative studies.

BIOLOGICALLY ACTIVE LUTEINIZING HORMONE (LH) IN PLASMA

1976 ◽  
Vol 83 (3) ◽  
pp. 454-465 ◽  
Author(s):  
P. Romaní ◽  
D. M. Robertson ◽  
E. Diczfalusy
Keyword(s):  
Menstrual Cycle ◽  
Dose Response ◽  
Gel Filtration ◽  
Biologically Active ◽  
Relative Potency ◽  
Response Curves ◽  
Plasma Pool ◽  
Dose Response Curves ◽  
Post Menopausal

ABSTRACT A recently described in vitro bioassay method for the measurement of biologically active LH (Van Damme et al. 1974) has been applied to the plasma of normally menstruating and post-menopausal women. The specificity of the procedure was established according to the following evidence: 1. Parallelism was observed between dose response curves obtained with serial dilutions of a standard LH preparation (HMG 2nd IRP) and plasma pools collected during the follicular phase, at the LH-peak, during the luteal phase and after menopause. 2. There was no evidence for the presence of any synergistic or antagonistic factor in the various plasma specimens. The assay design used to establish this consisted of assaying the standard and plasma pool separately and then together as a mixture followed by an asssessment of the difference (if any) in the potencies obtained. Strict additivity should yield a relative potency of 1.0. Plasma pools which were obtained every 2–3 days throughout the menstrual cycle were assayed using this design against the standard (HMG 2nd IRP) and against a mid-cycle plasma pool obtained at the time of the LH-peak. The latter was also assayed against partially purified plasma fractions obtained from a post-menopausal plasma pool after gel filtration and isoelectric focusing. With the exception of 3 assays, in which the estimates of relative potency were 0.91, 0.94 and 0.95, respectively, in 19 assays of additivity, the fiducial limits always included unity. 3. Non-detectable LH levels were found in the plasma or serum of either hypophysectomized or hypopituitary hypogonadal men or women treated with oestrogen/progestogen combined pills. 4. The presence of calf or human serum in the assay medium is an essential requirement for a valid comparison of standard and unknown preparations. In their absence, non-parallel dose response curves between plasma and standard were obtained. The other established criteria of reliability (sensitivity and precision) were also examined. The method is sufficiently sensitive (3.5–8.0 mIU/ml plasma; HMG (2nd IRP) as standard) for the measurement of LH throughout the cycle. The mean index of precision (λ) in 230 multiple assays was 0.040. It is concluded that the modified bioassay yields valid and reliable estimates of LH when applied to human plasma obtained throughout the menstrual cycle and after menopause.

scholarly journals Parameterizing Dose-Response Models to Estimate Relative Potency Functions Directly

2012 ◽  
Vol 129 (2) ◽  
pp. 447-455 ◽  
Author(s):  
Gregg E. Dinse ◽  
David M. Umbach
Keyword(s):  
Dose Response ◽  
Relative Potency ◽  
Response Models

A model-free approach to estimation of relative potency in dose-response curve analysis

1987 ◽  
Vol 252 (3) ◽  
pp. E357-E364 ◽  
Author(s):  
V. Guardabasso ◽  
D. Rodbard ◽  
P. J. Munson
Keyword(s):  
Dose Response ◽  
Goodness Of Fit ◽  
Nonlinear Least Squares ◽  
Relative Potency ◽  
Smoothing Spline ◽  
Enzyme Linked Immunosorbent Assay ◽  
Response Curves ◽  
Model Free ◽  
Dose Response Curves ◽  
Relative Potencies

We have developed a new, general approach to analysis of dose-response curves from bioassay, immunoassay (including radioimmunoassay, immunoradiouretic assay, enzyme-linked immunosorbent assay), and other experimental procedures. It provides a test for parallelism, similarity of shape, and a measure of relative potency for any set of two or more curves. The method uses a constrained smoothing spline function to estimate the curve shape, together with a nonlinear least-squares fitting technique to estimate parameters for relative potency and slope. The use of “constrained splines” permits the analysis of nonlinear dose-response curves that cannot be described by a simple model or equation such as the symmetric four-parameter logistic. A microcomputer program is used for the analysis, providing relative potencies and their SE and evaluation of goodness of fit

Eosinophilic bronchitis in asthma: A model for establishing dose-response and relative potency of inhaled corticosteroids

2006 ◽  
Vol 117 (5) ◽  
pp. 989-994 ◽  
Author(s):  
Margaret M. Kelly ◽  
Richard Leigh ◽  
Lata Jayaram ◽  
Charlie H. Goldsmith ◽  
Krishnan Parameswaran ◽  
...  
Keyword(s):  
Dose Response ◽  
Inhaled Corticosteroids ◽  
Relative Potency ◽  
Eosinophilic Bronchitis

THE CALCULATION OF THE DOSE-RESPONSE LINE IN QUANTAL ASSAYS WITH SPECIAL REFERENCE TO OESTROGEN ASSAYS BY THE ALLEN-DOISY TECHNIQUE

1952 ◽  
Vol 8 (2) ◽  
pp. 169-178 ◽  
Author(s):  
J. D. BIGGERS
Keyword(s):  
Maximum Likelihood ◽  
Special Reference ◽  
Effective Dose ◽  
Dose Response ◽  
Drug Action ◽  
Weighting Factor ◽  
Relative Potency ◽  
Method Of Maximum Likelihood ◽  
Response Line ◽  
Angular Transformation

A comparison has been made of the probit, logit, angular and rectangular transformations in the calculations of quantal dose response lines by the method of maximum likelihood. Data from Allen-Doisy oestrogen assays have been employed. Studies of the χ2 test for linearity and of the calculated median effective dose (m.e.d.) show no significant differences between the results obtained with any of the transformations. When group numbers are equal the angular transformation is the method of choice as the constant weighting factor reduces the amount of computation involved. The significance of these results, both in the calculation of the m.e.d. or relative potency and to the theory of drug action, has been discussed.

Determination of the Therapeutic Mean Effective Doses of Several Anti-inflammatory Agents in Adjuvant Arthritic Rats

1974 ◽  
Vol 52 (4) ◽  
pp. 791-796 ◽  
Author(s):  
R. R. Martel ◽  
J. Klicius ◽  
F. Herr
Keyword(s):  
Dose Response ◽  
Probit Analysis ◽  
Relative Potency ◽  
Response Curves ◽  
Treatment Groups ◽  
Clinical Observations ◽  
Inflammatory Drugs ◽  
Dose Response Curves ◽  
Anti Inflammatory ◽  
Therapeutic Test

The large variation in the severity of the arthritic response of the adjuvant-injected rat often makes it impossible to obtain statistically manageable dose–response curves with anti-inflammatory drugs. Consequently, the relative potency of anti-inflammatory drugs generally was not established. In the present study, with a modification of the therapeutic test, reliable dose–response curves were obtained with seven anti-inflammatory drugs. With this method the "therapeutic" mean effective dose (ED50) and relative potency were calculated by probit analysis. Charles River rats were injected in the left hind paw with adjuvant. On day 14, rats with an injected paw volume of 4–6 ml that increased by at least 0.5 ml between days 10 and 14 were selected for drug treatment. Groups of 6–12 rats with a mean injected paw volume of 5–5.5 ml were formed. Dosing with compounds was started on day 14 and continued daily until day 22 (nine injections). Ninety-four percent of the arthritic control rats showed a further increase in injected paw size between days 14 and 22 (mean, 1.06 ± 0.12 ml) whereas rats dosed with anti-inflammatory compounds showed a dose-related decrease in paw size during the same period. A decrease of 0.5 ml or more between days 14 and 22 was considered to be a therapeutic effect, smaller decreases were taken as no effect. The oral ED50's in milligrams per kilogram were indomethacin, 0.22 ± 0.05; prednisolone, 3.49 ± 1.0; hydrocortisone, 12.4 ± 3.0; phenylbutazone, 13.27 ± 2.7; mefenamic acid 20.10 ± 5.8; aminopyrine, 129.95 ± 25.3; and aspirin, 279.0 ± 24.6. Except for aspirin, the relative potency of the compounds studied by this therapeutic test (chronic) was comparable to that reported for the acute carrageenin assay. Aspirin appears to be markedly less active in chronic inflammation than in acute. This finding is consistent with both experimental and clinical observations.

Relative potency in nonsimilar dose–response curves

Weed Science ◽  
2006 ◽  
Vol 54 (3) ◽  
pp. 407-412 ◽  
Author(s):  
Christian Ritz ◽  
Nina Cedergreen ◽  
Jens Erik Jensen ◽  
Jens Carl Streibig
Keyword(s):  
Dose Response ◽  
Relative Potency ◽  
Response Curves ◽  
Dose Response Curves
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