Nifedipine absorption

Bode, H., E. Brendel, G. Ahr, U. Fuhr, S. Harder, and A. H. Staib. 1996. Investigation of nifedipine absorption in different regions of the human gastrointestinal (GI) tract after simultaneous administration of 13C and 12C nifedipine. Eur. J. Clin. Pharmacol. 50 195-201. 

J-F Westphal, J-H Trouvin, A Deslandes, C Carbon. Nifedipine enhances amoxicillin absorption kinetics and bioavailability in human. J Pharmacol Exp Ther 255 312-317, 1990. 

GI absorption of many poorly soluble drugs depends on small intestinal transit, as demonstrated for ketoprofen, nifedipine, haloperidol, miconazole, and others. Small intestinal transit rate and transit time become important factors in drug absorption, particularly when the ratio of dose to solubility is high and dissolution rate is very slow or when the drug is... 

Spasmolytics. N-Butylscopolamine (p. 104) is used for the relief of painful spasms of the biliary or ureteral ducts. Its poor absorption (N.B. quaternary N absorption rate <10%) necessitates parenteral administration. Because the therapeutic effect is usually weak, a potent analgesic is given concurrently, e.g., the opioid meperidine. Note that some spasms of intestinal musculature can be effectively relieved by organic nitrates (in biliary colic) or by nifedipine (esophageal hypertension and achalasia). 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

The sublingual surface area is relatively small but has a rich blood supply. The major advantage of this route is avoidance of intestinal destruction and hepatic first pass metabolism. However, absorption can be highly variable critical factors are the residence time of the drug in the mouth and saliva flow. Premature swallowing or excessive saliva production preclude efficient absorption. Nitroglycerin, nifedipine, propranolol, and buprenorphine are all available as sublingual preparations. Rectal... 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

The usefulness of action spectra can readily be seen in Figure 4. In these plots, it is readily demonstrated that the absorption spectrum is not a good indicator of the photosensitive wavelengths of nifedipine. These plots also demonstrate the... 

Teraoka R, Otsuka M, Matsuda Y. Evaluation of photostabUity of soUd-state nifedipine by using Fourier transformed reflection-absorption infrared spectroscopy. Photostability 99 3rd International Conference on the PhotostabiUty of Dmg Substances and Dmg Products, Washington, EX2, July 10-14,1999. 

Figure 7 Overiap region of the absorption spectrum of nifedipine and the output spectrum of sunlight.

Blue and colorless blisters had little photo protective effect on nifedipine tablets. Therefore, it is evident that the use of a blister of the proper color can be an effective photo protecting measure, but only if its absorption spectrum corresponds to that of the drug substance/product (Fig. 8) (20). 

Due to absorption of incident radiation in upper layers, the drug itself may have a photostabilizing effect. Photodegradation often leads to the production of colored products which themselves absorb and further shield the sample. Consequentially, degradation rates decrease with increasing concentrations as shown by the example of nifedipine solutions (Fig. 1) (3). 

Besides UV absorbers and food colorants, use of opacifiers is another way of photostabilizing photosensitive tablets. The protecting effect of yellow, red and black iron oxide could be shown for tablets containing the antiviral drug sorivudine, as well as molsidomine and nifedipine tablets (15). Iron oxides were found to be more effective than titanium dioxide, especially if the drug is particularly sensitive to radiation of wavelengths between 400 and 420 nm (e.g., nifedipine), where titanium dioxide shows an "absorption gap" (Thoma K, Aman W. In preparation) (4). 

Nifedipine. Solid dispersions of nifedipine with pyp[37] enteric polymers were evaluated in dogs and humans. PVP dispersions showed rapid absorption with a threefold increase in bioavailability when compared to physical mixtures. Sustained blood levels were obtained from solid dispersions with enteric polymers. 

It is obvious that drugs such as nifedipine and both isosorbide-5-mononitrate and isosorbide dinitrate, which have non-specific, wide absorption sites and so are well absorbed along the entire GI tract, may not be suitable candidates for GRDDS. Also, drugs that are irritant to the gastric mucosa " and those undergoing significant first-pass metabolism may have some limitations. Relevant examples of the latter type are nifedipine, propranolol, levodopa, diltiazem, metopro-lol and 5-fluorouracil. 

An active dipeptide transport system that depends on hydrogen ions takes up non-ester amino-beta-lactams (penicillin, amoxicillin, and oral first-generation cephalosporins) (337-339) and specific cephalosporins that lack the alpha-amino group (cefixime, ceftibuten, cefdinir, cef-prozil) (340,341). Nifedipine increases amoxiciUin and cefixime absorption, probably by stimulating the dipeptide transport system, since the serum concentrations of passively absorbed drugs and intestinal blood flow did not change (342-344). 

Westphal JF, Trouvin JH, Deslandes A, Carbon C. Nifedipine enhances amoxicihin absorption kinetics and bioavailabihty in humans. J Pharmacol Exp Ther 1990 255(1) 312-17. 

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