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First dose effect of dihydropiridine derivatives in hypertensive urgencies .Does sublingual way of drug administration exist in clinical setting?
R.Dąbrowski, Z.Sadowski, A.Goldnik, D.Marszałek, I.Kowalik, S.Jasek
Institute of Cardiology, Warsaw, Poland
The aim of the study was 10 assess plasma concentrations and influence of nifedipine 10mg [NIF] and nitrendipine 5mg [NIT], given sublingually [SL] and orally (swallowed) [PO] on systolic blood pressure reduction [SBPr], and heart rate [HR]. NIF and NIT were administered to 28 moderate hypertensive patients [pts], mean age 53 +/-11, body mass 79+/-13kg. Mean initial SBP and DBP values were: 167+/-9 and 108+/-9mmHg. BP was recorded for 24hrs using ambulatory BP monitoring (SpaceLabs 90207) with readings taken every 10min after placebo 10mg NIF or 5mg NIT in 2 ways, randomly, every 3 days. Plasma NIF and NIT [Cmax] levels were measured n 16 samples drawn for 8hrs after drug intake by HPLC method (sensitivity 2ng/ml).
Results: amount of the drug absorbed trough oral mucosa after 20 minutes was for NIF:
6.1mg (60.1%) and for NIT: 2.89ng/ml (57.8%). Mean values of serum concentrations; and SBP reduction after NIF and NIT administration:



time(h)

0.25

0.5

0-75

1

1.5

2

3

4

5

6


NIF-Cmax (mg/ml)

SL

12,7

21,1

27.2

28.3

27.7

19.3

12.6

13-0

6.4

6.1



PO

63,0

98,7

81.&

69.4

54.5

51.4

32.3

30.5

25.6

18.6


NIF-SBPr(%)

SL

7,1*

8,9*

7.4*

10.6*

6.9*

7.2^

6.4

6.2*

6.9*

3.1



PO

9.1**

17.2**

17.4**

16.7**

17.1**

19.1 **

17.0**

15.8**

16.4**

16.5**


NIT-Cmax (mg/ml)

SL

7.2

14.1

6.9

5.1

5.0

2.6

na

na

na

na



PO

14.5

19.0

20.1

22.2

17.4

16.9

14.4

8.8

6.6

4.4


NIT-SBPr(%)

SL

4.3

6.0

7.2

9.5

9.9*

10.1*

8.4

3.5

7.6

5.1



PO

6.3s

8.4*

12 I*

16 !•

14.4"

12.8*

17.2*

10.5"

162*

1617*


*p<0-05; **

p<0.001



After oral NIF and NIT administration plasma concentrations were significantly higher and caused more rapid, profound and prolonged SBP reduction. Patients were instructed to keep drugs in the month for 20 minutes (which was done with difficulty) and absorption was slow and led to low plasma levels. Normally, after initial biting a capsule the drug is swallowed with the saliva which results in higher and faster absorption in gastrointestinal tract.



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