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Dear All
I am wondering for the information regarding pharmacokinetic pharmacodynamic correlation for an antiasthmatic drug. The dose is administered by inhalation.
Thanks in anticipation
-- Regards
Rajendra H. Dhande.
Ph.D Student,
Department of Pharmacology and Toxicology,
Bombay College of Pharmacy, Mumbai,
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The following message was posted to: PharmPK
Rajendra,
> I am wondering for the information regarding pharmacokinetic pharmacodynamic correlation for an antiasthmatic drug. The dose is administered by inhalation.
> Most anti-asthma drugs given by inhalation have a topical effect so the systemic PK may be hard to measure because concs tend to be very low.
Beta-agonists are typically administered in doses that are several times the ED50 which means the effect is close to Emax. It is often hard to determine a dose effect relationship because the inhaler dose cannot be made small enough to explore in the region of the ED50 and below.
Nick
-- Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
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You may want to check these references.
1. Nebulized formoterol fumarate: Dose selection and pharmacokinetics.
Nicholas J. Gross et al. Pulmonary Pharmacology & Therapeutics 21 (2008) 818-823
2.Single-Dose Pharmacokinetics and Safety Pharmacodynamics of Formoterol Delivered by Two Different Dry Powder Inhalers. Journal of Aerosol Medicine and Pulmonary Drug Delivery. September 2008, 21(3): 309-320.
3. Biphasic Effect-Time Courses in Man after Formoterol Inhalation: Eosinopenic and Hypokalemic Effects and Inhibition of Allergic Skin Reactions.
Derks et al. JPET November 1, 1997 vol. 283 no. 2 824-832
Regards
Ganesh Mugundu
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The following message was posted to: PharmPK
Rajendra
Inhaled anti-asthmatic drugs are administered directly into the lungs at
very low doses. So, standard dose-exposure-response (PKPD)
methodologies, where the plasma concentrations (Cp) are used as the
forcing function for PD changes are not applicable for efficacy
biomarkers/endpoints because (1) Cp is "downstream" from efficacy, which
occurs in lungs and (2) doses are typically quite low (which is the
point of administering them directly to the site of action), so Cp is
typically not adequately characterisable.
However, we have successfully applied modelling methodologies to
longitudinal data to help with all stages of drug discovery and
development. Please refer to the following publications for details:
1. Agoram, Milligan, and van der Graaf (2008) Eur J Pharm Sci
(application in discovery)
2. Jacqmin et al (2007) JPKPD (the K-PD model, which allows you to model
PD data in the absence of PK data)
Balaji.
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