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Year : 1996  |  Volume : 50  |  Issue : 7  |  Page : 234-238

Bioequivalence studies of celiprolol in healthy human volunteers

Bombay College of Pharmacy, Kalina, Santacruz (E), Bombay-400 098, India

Correspondence Address:
E K Iyer
Bombay College of Pharmacy, Kalina, Santacruz (E), Bombay-400 098
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Source of Support: None, Conflict of Interest: None

PMID: 8979541

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How to cite this article:
Iyer E K, Tipnis H P. Bioequivalence studies of celiprolol in healthy human volunteers. Indian J Med Sci 1996;50:234-8

How to cite this URL:
Iyer E K, Tipnis H P. Bioequivalence studies of celiprolol in healthy human volunteers. Indian J Med Sci [serial online] 1996 [cited 2016 May 27];50:234-8. Available from:

 ¤ Introduction Top

Celiprolol is a hydrophilic β1 , selective adrenoceptor _antagonist with mild selective β2 , agonist as well as weak vasodilator proper­ties. It belongs to the third genera­tion of cardioselective beta ad­renoceptor antagonists and its profile indicates that it may lower blood pressure with less depres­sion of cardiac output than the beta blockers devoid of agonist activity, because of its ability to lower peripheral vascular resis­tance and minimum effect on rest­ing heart rate. A reduced potential to induce bronchoconstriction in asthmatic hypertensives and a pos­sible beneficial effect on serum lipid profile are other ancillary pro­perties that confer an advantage to it over existing beta blocker drugs. It is indicated in the treat­ment of patients with mild to mo­derate hypertension, systemic hypertension and annina pectoris. The starting dose of celiprolol is 200 mg with increase in dosage recommended upto 600 mg. Com­monly reported side- effects in­clude headache, - tiredness and fatigue. No reports of orthostatic hypertension or withdrawl sensiti­vity has been reported with celi­prolol. [1]

 ¤ Experimental Design Top

Drug Products : The present study included two formulations (400 mg tablets) of celiprolol. The products were coded in a double blind manner and were decoded only after the completion of the study. The two formulations were coded as A and B respectively.

Subjects : A single dose com­plete cross over study was carried out in twelve healthy human male volunteers in the age group of 20­-30 years and weighing between 55-60 kg., satisfying the standard criteria for health. Written consent was obtained from each volunteer prior to the study. Volunteers were fasted 12 hours prior to the admi­nistration of the drug and use of other drugs and stimulants (tea, coffee and alcoholic beverages) were forbidden prior to and during the study.

Protocol : A single dose (12 x 2) complete cross over design was followed as the study design. The volunteers were fasted overnight (12 hours) prior to the study. Zero hour fasting blood sample was withdrawn early morning. The formulations were administered as per the study design. Blood samples (5 ml) were withdrawn from the antecubital vein at intervals of 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 and 12.0 hours, in the post dosing period. The blood samples were centrifuged, the plasma was separated and stored at -20°C until analysis. The volunteers refrained from strenuous activities during the course of the study. Standard breakfast and lunch was provided at 2.0 and 6.0 hours post-dosing and two consecutive runs were separated by a washout period of fifteen days.

Analysis of Celiprolol from Plasma : A RP-HPLC method developed by Buskin et al [2] was used to quantitate plasma levels of celiprolol. Spiked plasma samples were measured intermittently as external standard.

Statistical Data Analysis : The mean peak plasma levels of celiprolol (Cmax) and mean time to achieve these peak levels (Tmax) were computed directly from plasma level profiles as a measure of the rate of absorption of the drug from each product. The elimination rate constant (Kel) was calculated from the terminal elimination phase of log plasma concentration versus time plot by the method of least square regression analysis. [3]

From the slope of the regressionline, Kel was calculated as

Kel = 2.303 X slope

Biological half life (T½) was determined by the formula

½ = 0.693/Kel.

The extent of absorption for both the products in the volunteers was calculated from the area under the plasma concentration time curve from time curve 0 to 12 hours by the trapezoidal rule method. Area under the plasma concentration time curve from time zero to infinity was calculated using the relation.

AUCO-d) AUC 0-12 + C12/Kel. where C12 = drug concentration in the plasma at 12 hours.

The various pharmacokinetic parameters were subjected to ANOVA [4] (Analysis of Variance) at 95% confidence interval. The statistical significance between the products and the volunteers were also evaluated.

 ¤ Results Top

The mean plasma levels of celiprolol alongwith the various pharmacokinetic parameters obtained following the administration of both the products are given in [Table 1]. Results of the pooled -t test and the two way ANOVA of the various pharmacokinetic parameters of celiprolol tablets are shown in [Table 2].

 ¤ Conclusion Top

From the study it can be con­cluded that the two products A and B of celiprolol formulation tablets can be considered bioequivalent since there is no significant diffe­rence in various pharmacokinetic parameters between the two pro­ducts.

 ¤ Summary Top

Thus bioequivalence between the two products was established by undertaking this study. From [Table 1] it can be seen that the standard deviation at the various sampling points is high indicating varying absorption rates in indivi­dual volunteers, but this was ob­served in case of both the pro­ducts. Also, since the study design was complete crossover this high standard deviation was not due to any study design variable. As celi­prolol shows non-linear [1] dose re­lated absorption kinetics this high value of standard deviation may be due to the intersubject variation during the absorption process. However all the pharmacokinetic parameters showed a comparable profile when statistically evaluated for any significant difference bet­ween the two products.

 ¤ Acknowledgements Top

The authors wish to thank M/s Rhone Poulenc India Limited for supply of pure drug, formulations and financial assistance rendered for the study.

 ¤ References Top

1.Buckley MT, Miluve RJ. Drugs, 1991;41:941-969.  Back to cited text no. 1      
2.Buskin J. N. et al. J. Chromatogr 1982;230:454-460.  Back to cited text no. 2      
3.Speigel MR. Curve Fitting, Method of Least Squares and Correlation Theory. In Schaum's Outline Series, Theory and Problems of Statistics, McGraw Hill Book Co. NY First ed. 1972;PP 217.  Back to cited text no. 3      
4.Gupta CB, Gupta V. in Analysis of Variance (ANOVA), An Introduc­tion to Statistical Methods, Eigh­teenth Revised Edition Vikas Pub­lishing House Pvt Ltd New Delhi. 1992;pp 658.  Back to cited text no. 4      


  [Table 1], [Table 2]


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