Pharmacokinetics and pharmacodynamics of crushed and intact nifedipine prolonged-action (AdalatRTM PA) tablets in healthy male volunteers

Short-acting nifedipine capsules are discouraged for the treatment of acute asymptomatic hypertension (HT) due to serious adverse events associated with precipitous BP reduction. While intact nifedipine PA tablets provide a more gradual and sustained BP reduction, the antihypertensive properties of crushed PA tablets for nasogastric (NG) administration are unknown. The pharmacokinetics [area under the curve (AUC), peak concentration (Cmax), time to peak concentration (Tmax), absorption rate (Ka), half-life] and pharmacodynamics (magnitude and duration of BP reduction) of single-dose intact and crushed nifedipine PA 20 mg tablets in 21 healthy, male volunteers were compared in a randomized, open-label, crossover study. Data are presented as mean ± SD. <table cwl="104:85:95:69" wdm="100" dispwid="5.99in"><rowrule rty="."> <tablerow rht="0.18in"><cellrule rty="."> <tablecell></tablecell> <cellrule rty="."> <tablecell>Intact Tablet</tablecell> <cellrule rty="."> <tablecell>Crushed Tablet</tablecell> <cellrule rty="."> <tablecell>P-Value</tablecell> <cellrule rty="."></tablerow> <rowrule rty="-"> <tablerow><cellrule rty="."> <tablecell>AUC0-[infinity] (ng*min/ml)</tablecell> <cellrule rty="."> <tablecell chj="c">207.2 ± 87.6</tablecell> <cellrule rty="."> <tablecell chj="c">254.2 ± 108.5</tablecell> <cellrule rty="."> <tablecell chj="c">0.0001</tablecell> <cellrule rty="."></tablerow> <rowrule rty="."> <tablerow><cellrule rty="."> <tablecell>Cmax (ng/ml)</tablecell> <cellrule rty="."> <tablecell chj="c">32 ± 14</tablecell> <cellrule rty="."> <tablecell chj="c">40 ± 14</tablecell> <cellrule rty="."> <tablecell chj="c">0.0003</tablecell> <cellrule rty="."></tablerow> <rowrule rty="."> <tablerow><cellrule rty="."> <tablecell>Tmax (min) </tablecell> <cellrule rty="."> <tablecell chj="c">112 ± 54</tablecell> <cellrule rty="."> <tablecell chj="c">96 ± 45</tablecell> <cellrule rty="."> <tablecell chj="c">NS</tablecell> <cellrule rty="."></tablerow> <rowrule rty="."> <tablerow><cellrule rty="."> <tablecell>Ka (min-1)</tablecell> <cellrule rty="."> <tablecell chj="c">0.055 ± 0.051</tablecell> <cellrule rty="."> <tablecell chj="c">0.063 ± 0.137</tablecell> <cellrule rty="."> <tablecell chj="c">NS</tablecell> <cellrule rty="."></tablerow> <rowrule rty="."> <tablerow><cellrule rty="."> <tablecell>[Delta] SBP (mmHg)</tablecell> <cellrule rty="."> <tablecell chj="c">-14.0 ± 6.4</tablecell> <cellrule rty="."> <tablecell chj="c">-11.3 ± 6.0</tablecell> <cellrule rty="."> <tablecell chj="c">NS</tablecell> <cellrule rty="."></tablerow> <rowrule rty="."> <tablerow><cellrule rty="."> <tablecell>[Delta] DBP (mmHg)</tablecell> <cellrule rty="."> <tablecell chj="c">-10.8 ± 5.9</tablecell> <cellrule rty="."> <tablecell chj="c">-9.1 ± 5.4</tablecell> <cellrule rty="."> <tablecell chj="c">NS</tablecell> <cellrule rty="."></tablerow> <rowrule rty="-"> No significant differences were observed between the intact and crushed PA tablets with respect to the magnitude and duration of BP reduction, rate of absorption and elimination. Crushed PA tablets resulted in greater absorption as reflected in the higher AUC and Cmax. 'Conclusion'. The small difference in serum nifedipine concentration between the crushed and intact PA tablets did not result in clinical or statistical differences in BP reduction. Crushed nifedipine PA tablets provide a therapeutic alternative in the treatment of acute HT.