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raghavendra_s ★ 2010-05-12 13:16 (5886 d 19:08 ago) Posting: # 5332 Views: 4,858 |
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Dear Madam/Sir, I would like to know the issues involved in the design of Alendronate sodium for two treatment, two period, two sequence, single dose, crossover bioequivalence study. Please clarify me the issues associated with sampling (plasma/serum or urine)? which one is best to quantify the drug, serum/plasma or urine? How it impact the study design? In the published literature, the number of volunteers too largely vary from one article to another. How much sample size is required? statistical parameters etc. What is the washout period for this study ? It seems only HPLC-Fluorescence detection technique is available for estimation of the drug. Is there any updates on analytical developments of this drug in serum? Any discussion on further updates, technical aspects on this study design is highly appreciated? Kind regards, |
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Helmut ★★★   Vienna, Austria, 2010-05-12 17:38 (5886 d 14:46 ago) @ raghavendra_s Posting: # 5333 Views: 4,282 |
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Dear Raghavendra! ❝ Please clarify me the issues associated with sampling (plasma/serum or ❝ urine)? which one is best to quantify the drug, serum/plasma or urine? Depends.  FDA (draft 2008) suggests urine. In the EU urine data are only acceptable in exceptional cases (due to analytical limitations). Even if you opt for a multiple dose study or SD in urine, EMA want's to see Cmax in plasma. See the current guideline (Section "The use of urinary data"). Though MAs were granted in the past based on urinary data (Sweden 2008), plasma was used in more recent ones (UK 2009). ❝ In the published literature, the number of volunteers too largely vary ❝ from one article to another. How much sample size is required? Not uncommon, especially for such a drug (clinical setting, sampling procedures & intervals, bioanalytical methods). I would opt for a pilot study. ❝ It seems only HPLC-Fluorescence detection technique is available for ❝ estimation of the drug. Is there any updates on analytical developments of ❝ this drug in serum? In the UK-application LC/MS-MS was employed. Other methods may be used after adaption (see here for GC/MS of clodronate). — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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raghavendra_s ★ 2010-05-12 19:06 (5886 d 13:18 ago) @ Helmut Posting: # 5334 Views: 4,124 |
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Dear sir, The submission authority is in South East Asia, probably either in Singapore or India. Kind regards, |
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jchapdelaine ☆ 2010-05-13 00:16 (5886 d 08:07 ago) @ raghavendra_s Posting: # 5336 Views: 4,097 |
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Regarding the use of plasma or urine, originally it was not possible to analyze the plasma levels due to sensivitiy issues for bisphosphonates. However labs now have the sensitivity to analyze plasma PK profiles. Last year I discussed with FDA why for alendronate it is recommended to analyze in urine when plasma is available. The response was that it is an old recommendation, and that if plasma PK analysis is possible, then this should be used. My lab currently has a method for both plasma and urine analysis, however as of now, sponsors have only used the urine method. |
Ing. Helmut Schütz