STATISTICAL INFERENCE FOR RELATIVE POTENCY IN BIVARIATE DOSE-RESPONSE ASSAYS WITH CORRELATED RESPONSES

2005 ◽  
Vol 15 (2) ◽  
pp. 343-351 ◽  
Author(s):  
Stephen J. Iturria
Keyword(s):  
Statistical Inference ◽  
Dose Response ◽  
Relative Potency ◽  
Correlated Responses

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.

Comparing two statistical models for low boom dose-response relationships with correlated responses

2021 ◽  
Vol 150 (4) ◽  
pp. A260-A260
Author(s):  
Aaron B. Vaughn ◽  
William Doebler ◽  
Kathryn Ballard ◽  
Jonathan Rathsam
Keyword(s):  
Dose Response ◽  
Statistical Models ◽  
Correlated Responses

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
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