Evaluation of the Pharmacokinetics and Safety of Ascending Single Oral Doses of GR43175 Administered to Healthy Male Volunteers

Busch, Michael; Plachetka, John R.; Donn, Karl H.; Hussey, Betty; Clements, Bill; Leese, Philip T.

doi:10.1177/0333102489009s10219

Cited by 5 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, we found that the stressed and non-stressed encapsulated sumatriptan had mean AUC of 203.98 and 199.74 ng h/ml, respectively. Both of these values also are within the range of 128-419 ng h/ml reported previously for standard sumatriptan [1,14,17,19].…”

Section: Discussionsupporting

confidence: 89%

“…We also found that the stressed and non-stressed encapsulated dosage forms of sumatriptan had a mean T max of 1.98 and 1.83 h, respectively. Both of these values are within the range of 1.2-2.3 h reported previously for standard sumatriptan [1,14,16,17,19]. Finally, we found that the stressed and non-stressed encapsulated sumatriptan had mean AUC of 203.98 and 199.74 ng h/ml, respectively.…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan

Milton

Kleinermans

Scott

et al. 2001

International Journal of Pharmaceutical Medicine

View full text Add to dashboard Cite

The bioequivalence of encapsulated vs standard (commercial) sumatriptan was assessed before comparative eletriptan-sumatriptan efficacy studies in the acute treatment of migraine were conducted. Commercially acquired sumatriptan was encapsulated to ensure the double-blind nature of these studies.The pharmacokinetics of three single oral doses of sumatriptan 100 mg -the standard tablet, an encapsulated tablet, and a stressed encapsulated tablet -were compared in an open, randomized, three-way crossover study. Stressed capsules were produced by storing capsules for 12 weeks at 40 C/75% humidity; conditions chosen to accelerate any effects potentially induced by long-term storage under normal conditions. Blood samples were obtained from 22 males at baseline and at intervals over 24 h post-dose. Bioequivalence parameters were calculated as mean ratios and associated 90% confidence intervals, and between-drug differences were assessed using standard criteria. A prior in vitro dissolution study confirmed similar dissolution of the encapsulated and standard forms; though stressed tablets had decreased dissolution.For standard, encapsulated and stressed encapsulated sumatriptan, the area under the plasma concentration-time curve from 0 to infinity (AUC) values were 201.95, 199.74 and 203.98 ng h/ml, respectively. Maximum observed plasma concentration (C max ) values were 58.91, 56.09 and 52.56 ng/ml, respectively. The times to the first occurrence of C max (T max ) were 1.69, 1.83 and 1.98 h, respectively. All forms were bioequivalent using the standard range of 80-125%, with the exception of a 1% out of range C max for the stressed form. This parameter was within range using C max /AUC, a more sensitive absorption rate estimate.These results demonstrate that the encapsulated and stressed sumatriptan used in these studies are bioequivalent to commercial sumatriptan. The T max data suggest a similar rate of absorption.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan

Milton

Kleinermans

Scott

et al. 2001

International Journal of Pharmaceutical Medicine

View full text Add to dashboard Cite

show abstract

“…On the other hand, 40% of the total dose of oral sumatriptan is excreted in feces and the remainder in urine. Urinary elimination consists of both the indole acetic metabolite as well as the unchanged drug 34,40–43,54–57,81,82,87,91–93,104–108…”

Section: Overview Of Pharmacokinetics Of Sumatriptan–naproxenmentioning

confidence: 99%

Sumatriptan-naproxen fixed combination for acute treatment of migraine: a critical appraisal

Khoury

Couch²

2010

DDDT

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs (NSAIDs), including naproxen and naproxen sodium, are effective yet nonspecific analgesic and anti-inflammatory drugs, which work for a variety of pain and inflammatory syndromes, including migraine. In migraine, their analgesic effect helps relieve the headache, while their anti-inflammatory effect decreases the neurogenic inflammation in the trigeminal ganglion. This is the hypothesized mechanism by which they prevent the development of central sensitization. Triptans, including sumatriptan, work early in the migraine process at the trigeminovascular unit as agonists of the serotonin receptors (5-HT receptors) 1B and 1D. They block vasoconstriction and block transmission of signals to the trigeminal nucleus and thus prevent peripheral sensitization. Therefore, combining these two drugs is an attractive modality for the abortive treatment of migraine. Sumatriptan–naproxen fixed combination tablet (Treximet® [sumatriptan–naproxen]) proves to be an effective and well tolerated drug that combines these two mechanisms; yet is far from being the ultimate in migraine abortive therapy, and further research remains essential.

show abstract

“…Even if encapsulation had delayed the dissolution of the 100‐mg sumatriptan tablet, which it did not, it would have been unlikely to yield a significant difference in therapeutic efficacy. Commercially available sumatriptan exhibits low (14%) oral bioavailability, and tablet absorption tends to be relatively variable and unpredictable, with C max following a 100‐mg oral dose ranging among studies from 43 to 78 ng/mL, a median or mean time to C max (t max ) in the range of 1.2 to 2.3 hours, and a mean AUC in the range of 128 to 419 ng•h/mL 18–22 . The reported variability in the pharmacokinetics of oral sumatriptan is also apparent in the US product labeling, which indicates that the 100‐mg dose has a mean C max of 51 ng/mL, with a range of 28 to 100 ng/mL 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Commercially available sumatriptan exhibits low (14%) oral bioavailability, and tablet absorption tends to be relatively variable and unpredictable, with C max following a 100-mg oral dose ranging among studies from 43 to 78 ng/mL, a median or mean time to C max (t max ) in the range of 1.2 to 2.3 hours, and a mean AUC in the range of 128 to 419 ng•h/ mL. [18][19][20][21][22] The reported variability in the pharmacokinetics of oral sumatriptan is also apparent in the US product labeling, which indicates that the 100-mg dose has a mean C max of 51 ng/mL, with a range of 28 to 100 ng/ mL. 23 At sumatriptan doses of 50 mg or higher, the variability in absorption does not appear to influence efficacy because there is no significant dose-response or concentration-response relationship at doses ranging from 50 to 300 mg. 9,24 Given that there is only a small (7%) decrease in efficacy at the 25-mg dose, 9 it appears that the concentration required for maximal efficacy (E max ) reaches the asymptotic portion of the doseresponse curve (ie, plateau) somewhere near the C max of the 50-mg dose (29 ng/mL).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Disintegration Profiles of Encapsulated and Nonencapsulated Sumatriptan: Gamma Scintigraphy in Healthy Volunteers

Wilding¹,

Clark²,

Wray³

et al. 2005

The Journal of Clinical Pharma

View full text Add to dashboard Cite

The goal of this exploratory pilot study was to use gamma scintigraphy to evaluate, under physiological conditions, disintegration profiles of encapsulated and nonencapsulated formulations of 100 mg sumatriptan. Using a crossover design, healthy volunteers (n = 10) ingested 100-mg doses of sumatriptan tablets radiolabeled with 111Indium, as well as encapsulated sumatriptan tablets that were prepared similarly, then placed within a gelatin capsule and backfilled with an excipient blend radiolabeled with 99mTechnetium. A gamma camera recorded scintigraphic images until 5 hours postdose. Initial disintegration of the gelatin capsule was observed at a mean (range) of 5 minutes (1-11 minutes); disintegration was complete within 14 minutes (5-24 minutes). For nonencapsulated versus encapsulated tablets, the mean (+/- standard deviation) time to initial disintegration (6 +/- 5 minutes vs 8 +/- 5 minutes) and time to complete disintegration (18 +/- 14 minutes vs 16 +/- 7 minutes) were comparable. Results of this study demonstrate that encapsulated and nonencapsulated sumatriptan have equivalent in vivo dissolution rates.

show abstract

Evaluation of the Pharmacokinetics and Safety of Ascending Single Oral Doses of GR43175 Administered to Healthy Male Volunteers

Cited by 5 publications

References 0 publications

The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan

The bioequivalence of standard sumatriptan tablets and two encapsulated forms of sumatriptan

Sumatriptan-naproxen fixed combination for acute treatment of migraine: a critical appraisal

In Vivo Disintegration Profiles of Encapsulated and Nonencapsulated Sumatriptan: Gamma Scintigraphy in Healthy Volunteers

Contact Info

Product

Resources

About