NONINVASIVE AMBULATORY BLOOD PRESSURE MONITORING AFTER ADMINISTRATION OF ACE-INHIBITOR/CCB AND THEIR COMBINATION

Pharma Admission

igmpi

pharma admission

igmpi

 

The T/P ratios of the treatment groups were calculated by dividing the average change in trough systolic and diastolic pressure by the average change in peak systolic and diastolic pressure. All subjects were included in this analysis. In each treatment group the T/P ratio was greater than 0.5 except in co-administration treatment group, where DBP was found to be lesser than 0.5 (Table 2).According to US FDA proposed guidelines for the clinical evaluation of new antihypertensive drugs, suggesting that the drug effect at trough should be not less than half to two thirds of the peak (US DHHS, 1988). In this clinical study, results showed that co-administration reduces the ambulatory blood pressure more potentially than monotherapy in daytime. But the monotherapy produced a homogenous ambulatory blood pressure control over the 24-hours than co-administration therapy. As T/P ratio was observed greater with respect to monotherapy in comparison to co-administration therapy.

Lercanidipine 10 mg and imidapril 5 mg were well tolerated when administered either alone or co-administered. Calamine lotion was given to a subject who was on co-administration therapy and developed rashes on his back which was further subsidized after its application. Except that, only few cases of study drugs related mild adverse events were observed which were further resolved without anysequelae or need for drug treatment. All adverse events intended to study medications are summarized in table-2.

BP measurement with ABPM device had several potential advantages over sphygmomanometer BP measurement, which includes - No observer bias or digit preference, greater reproducibility, little or no white-coat hypertension effects, easy to differentiate dipper and non-dipper hypertensive subjects and assessment under conditions of daily life for full 24 hour period.

CONCLUSION
In conclusion, the results of present study showed that all study treatments were effective in lowering ambulatory blood pressure in subjects with the essential hypertension, but co-administration therapy was significantly more effective than monotherapy.

However, the treatment with higher trough/peak ratio (monotherapy) produces a much more consistent effect over 24 hours. In comparison, co-administration produces a profound fall in blood pressure around the time of peak response which then tails off towards the trough effect at the end of the dose. Furthermore, a direct comparison of monotherapy and co-administration demonstrated superiority for monotherapy with respect to trough/peak ratio.

In respect to monotherapy, comparatively less adverse events were occurred in a group who received co-administration therapy. Therefore, it shows that the improved efficacy with co-administration was not associated with a worse tolerability of the treatment.

Finally, it concludes that lercanidipine 10 mg and imidapril 5 mg may be an effective combination for the treatment of essential hypertensive subjects. Further, additional clinical studies for the evaluation of this combination are warranted on larger pool of hypertensive subjects.

Figure-1

Study design


Where, Treatment I/P = Imidapril (5 mg) + Placebo (10 mg); Treatment L/P = Lercanidipine (10 mg) + Placebo (5 mg); Treatment I/L = Imidapril (5 mg) + Lercanidipine (10 mg).

Figure-2

Mean change in ABPM systolic and diastolic blood pressure from baseline after one week of treatments


[Where, Imi = Imidapril (5 mg); Ler = Lercanidipine (10 mg)]

Figure-3

Systolic (upper panel) and diastolic (lower panel) blood pressure profile during baseline (B) and post treatment with Lercanidipine (L), Imidapril (I) and Co-administration (I/L)


Figure-4

Normalization rates according to ABPM reading at trough

 

Pharmacodynamic

Parameters

TREATMENT-A

TREATMENT-B

TREATMENT-C

Baseline

(N=14)

Imi 5mg + Placebo

(N=14)

Baseline

(N=13)

Ler 10mg + Placebo

 (N=13)

Baseline (N=13)

Ler 10mg+

Imi 5mg

(N=13)

ABPM 24 h SBP

129±9

125±7**

133±8


126±6**

132±7


123±6**

ABPM

24 h DBP

86±7

82±5**

87±7

83±5**

86±7

79±5**

Daytime SBP

134±3

129±4**

137±2

129±3**

136±2

125±5**

Daytime DBP

90±2

85±3**

90±2

85±3**

89±2

81±4**

Night-time SBP

118±5

116±4^

122±6

119±5*

123±7

118±5*

Night-time DBP

77±5

76±5^

78±6

77±4^

77±5

74±5*

Table-1

Ambulatory BP during baseline and post  treatment with imidapril 5 mg,       lercanidipine 10 mg and their co-administration for period of one week (Mean±SD)

** Highly Significant (P<0.01); * Significant (P<0.05); ^ Not Significant (P>0.05) as compared to respective baseline value.

Table-2

Trough/Peak ratio index in the three treatment groups after 1 week of treatment

SL No.

Index

Imidapril

lercanidipine

Imidapril + lercanidipine

1.

SBP Trough/Peak Ratio

0.75

0.54

0.52

2.

DBP Trough/Peak Ratio

0.58

0.56

0.38

REFERENCE
1. Puig, J. G., Calvo, C., Luurila, O., Luurila, H., Sulosaari, S., and Strandberg, A. (2007) ‘Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo controlled, randomised, crossover study with four ABPM’ Journal of Human Hypertension 21, 917-24
2. Miller-Craig, M., Shaffu, B., Greenough, A., Mitchell, L., and McDonald, C. (2003) ‘Lercanidipine vs lacidipine in isolated systolic hypertension’ Journal of Human Hypertension 17, 799-806
3. Ding, P, Y-A., Chu, K-M., Chiang, H-T., Shu, K-H. (2004) ‘A double-blind ambulatory blood pressure monitoring study of the efficacy and tolerability of once-daily telmisartan 40 mg in comparison with losartan 50 mg in the treatment of mild-to-moderate hyoertension in Taiwanese patients’ Int J Clin Pract 58, (Suppl. 145) 16-22
4. Naidu, M. U. R., Usha, P. R., Rao, T. R. K., and Shobha, J. C. (2000) ‘Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension’ Postgrad Med J 76, 350-53
5. Kohlmann, O. Jr. (2006) ‘The “LOTHAR” Study: Evaluation of efficacy and Tolerability of the Fixed Combination of Amlodipine and Losartan in the Treatment of Essential Hypertension’ Arquivos Brasileiros de Cardiologia 86, N0 1
6. Fogari, R., Mugellini, A., Zoppi, A., Lazzari, P., Destro, M., and Rinaldi, A. (2006) ‘Effect of telmisartan/ hydrochlorothiazide vs. lisinopril/ hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients’ J Hum Hypertens 20, (3) 177-85
7. Ragot, S., Sosner, P., Yau, C., Brunel, P., and Herpin, D. (2006) ‘Management in general practice of hypertensive patients poorly controlled with a fixed-dose renin–angiotensin system inhibitor and diuretic combination: results from a French national survey’ J Hum Hypertens 20, (6) 407-18
8. Rump, L. C., Ambrosioni, E., Burnier, M., Horl, W., and Rabelink, A. J. (2006) ‘Initial combination therapy with olmesartan/hydrochlorothiazide in moderate-to-severe hypertension’ J Hum Hypertens 20, (4) 299-301
9. Whitworth, J. A. (2003) ‘World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension’ J Hypertens 21, (11) 1983-92
10. Omboni S., Parati G., Zanchetti A., Mancia G. (1995) ‘Calculation of trough:peak ratio of antihypertensive treatment from ambulatory blood pressure. Methodological aspects. J Hypertens 13:1105-1112
11. Food and Drug Administration, Proposed Guideline for the Clinical Evaluation of Anti-Hypertensive Drugs. Rochville, MD: Division of Cardio-Renal Drug Products, US Department of Health and Human Services, 1988

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