前幾篇的內容是:降磷的三大重點、透析清除磷離子的極限、使用鋁片的隱憂、以及使用鈣片的注意事項,這篇把重點放在自費降磷藥物,有兩種,它們不含鈣、也不含鋁,因此,沒有吸收鈣過量或鋁中毒的這些疑慮,那麼,它們有什麼特別之處呢?
Sevelamer (中文藥品名:磷能解、磷減樂、腎安磷等)
這是第一個問世的“不含鋁、不含鈣”的磷結合劑,有趣的是,原本它是設計用來降血脂肪的,卻發現它有降磷的效果。這個物質,是個大分子聚合物,分子量是10000000000000000,別數了,一共有16個零,夠大了吧,大到腸道沒辦法吸收,所以它沒有累積體內的問題。
1998年,美國FDA正式認可這個藥物 (sevelamer hydrochloride,磷能解、腎安磷),可供降磷之用,後來有些患者發生了酸中毒,藥廠把後頭的氫氯酸根,修正為碳酸根,變成“磷減樂”(sevelamer carbonate),就不會有酸中毒的情況了。由於真正降磷的主角是sevelamer,因此,從治療效果來看,兩者並無差別。
它的特點,除了前面所說的:可以降低血脂肪(特別是低密度膽固醇,又稱壞的膽固醇)、不被身體吸收之外,另外要注意的是,這個大分子是個陰離子交換樹脂,白話一點說,這個龐然大物,只要遇到身上帶負電的,全部都會被它吃掉,除了磷之外,葉酸、脂溶性維他命(D、E、K,尤其維他命D對於腎友很重要)、或者一些常見的藥物,都會被它影響,而導致體內藥物濃度下降,因此,在使用這個藥物時,要注意其他藥物的反應,是否有減弱的情形。
有腎友問到,哪些藥物會受影響,除上述維他命之外,比較明顯的是ciprofloxacin[一種廣效的抗生素,藥物濃度會下降近50%],其他有研究的藥物倒不明顯。如果有用該藥物的話,建議在吃磷減樂之前一個小時吃,或者磷減樂之後三個小時吃,比較不會影響吸收。
Lanthanum (碳酸鑭,中文藥品名:福斯利諾)
2004年,FDA核准這個藥物可用於慢性腎臟病患者,鑭這個元素為稀土元素,離子態都是帶正電三價 (附帶一提,鋁也是帶正電三價,磷酸鹽是負電三價,可能是因為如此,他們結合磷的能力,都比帶正電兩價的鈣來的好)。碳酸鈣的結合力會受胃酸影響,但碳酸鑭不會,從pH值1-7都有不錯的結合力。
碳酸鑭非常難溶於水,只有百分之0.001會被腸道吸收 (鋁片則是百分之0.1會被吸收),因此,累積在體內的量比鋁少很多很多。另外,鑭這個元素會被擋在腦膜外面(BBB,blood brain barrier),因此,鋁中毒那種腦病變,碳酸鑭沒有。至於鋁所造成的骨頭沉積病變(osteomalacia),到目前為止,使用碳酸鑭的腎友,骨頭雖然有沉積鑭元素,但是骨頭的活性各方面,是沒有受影響的。
碳酸鑭對於脂溶性維他命的吸收,或者藥物之間的交互作用,可以說是沒有影響,因此,副作用也少的情況下,使用上很單純,降磷效果好。
新藥 V.S 舊藥
新藥的優勢,在於本身不含鈣,使得腎友產生高血鈣的機會較低,因此血管鈣化情況較少,甚至能夠降低血管的硬化程度,sevelamer(磷能解等)甚至還能夠降低壞膽固醇,把這些優點分析起來,是非常有機會能夠降低死亡率的……但是早期大部分研究都說,與鈣片的差距仍然拉不開。
直到2013年,一篇整合分析(meta-analysis)的文章,發表在 Lancet,指出:使用新藥的腎友,能夠比使用鈣片的腎友,死亡率降低22%(95% CI 0·61–0·98),這才讓大家長久以來的猜測,獲得證實。
因此,醫界普遍認為,避免接觸鋁、以及盡量降低身體鈣的負擔,對身體長遠來說,仍然會看到好處,這些就是新藥的優勢。
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http://doi.org/10.1016/S0140-6736(13)60897-1