Page 58 - Numero20-2_2017

optimal level of metabolism of the substrate drug and the individual's response to that particular medication.
4. Inducers: A molecule (a drug or herb) that starts expression of the gene that encodes the enzyme.
The commonly used Chinese herbs that are identified as the inhibitor or inducer of a CYP 450 isoform have been summarized in the following tablet. When a Chinese herb acts as an inhibitor, it will inhibit the activity of the affected CYP450 isoform and may decrease the metabolism of the drug on which the affected CYP450 isoform act, thus may increase the bioavailability of the drug. When a Chinese herb acts as an inducer, it will increase the activity of the affected CYP450 isoform and may increase the metabolism of the drug on which the affected CYP450 isoform acts, thus may decrease the bioavailability of the drug.
together with drugs which are known substrates of affected isoenzymes.
2.4 Elimination
Factors that affect the GI elimination of herbs or drugs include GI motility and intestinal flora. GI motility is the primary factor in this regard. Kidney elimination is another important factor of herb or drug excretion. Theoretically any substance that may change any of above factors may interfere the clearance of other substance (drugs or herbs) from the kidney. It depends on health of the kidneys, organ maturity, volume of distribution, perfusion of the kidneys and urinary pH.
In patients with impaired kidney function, the rate of elimination by the kidneys would be significantly slow down leading to an accumulation of herbs and drugs in the body. As a safety precaution, it may be necessary to lower the dose of herbs to avoid unnecessary and unwanted side-effects in following patients.
- Patients on dialysis
- Patients with transplant of kidney
- Patients taking some drugs that damage the kidneys such as amphotericin B, methotrexate, tobramicin and gentimicin.
The elimination of some drugs from kidneys is also associated with pH value of urine. There is no any clinical report about the association between urine acidity changes due to herbal use and changes of drug elimination and renal re- absorption. Generally when urine is acidic, weak acid drugs tend to be reabsorbed. Alternatively when urine is more alkaline, weak bases are more extensively. The renal clearance of drugs such as NSAIDs (pKa3-8) and morphine analogs and tricyclic antidepressants (pKa 6-12) is often dependent on urine pH.
The first group is the herbs that may decrease the acidity of urine. They include Hai Gai Ke (clam shell), Hai Piao Xiao (cuttlefish bone), Mu Li (oyster shell), and Long Gu (dragon bone). The renal re-absorption of some drugs may be increased in the alkalized urine, which may theoretically increase the risk of overdose toxicity. Alkaline urine (pH >6.0) increases crystal precipitation within tubular lumens from drugs such as indinavir, oral sodium phosphate solution, and ciprofloxacin (30,31,32).The above mentioned herbs should not be used together with these drugs.
The second group of herbs may increase the urine acidity and they are often high in organic acids. They include Shan Zhu Yu, Nu Zhe Zi, Jin Yin Zi, Fu Peng Zi, Qing Pi, Chen Pi, Wu Wei Zi, Wu Bei Zi, Bao Shao Yao, Jin Ying Hua, Wu Mei, Shan Za, Zhi Shi, Zhi Ke, and Mu Gua. For example, acidic urinary pH (<5.5) increases crystal deposition with drugs such as sulfadiazine, methotrexate, and triamterene that are insoluble in a low pH environment (30.31). These acidity- increasing herbs should not be used together with these drugs. The increased crystal deposition due to decreased pH of urine (acidic urine) may theoretically cause the damage of epithelium cells in urinary system, and causes the crystals in urine and hematuria.
Summary of CYP450 Isoforms and Herb- Drug Interactions
Note: If an herb is an inhibitor of an isoform, then the clinical effectiveness of the drug (substrate) metabolized by the isoform may increase due to the inhibited isoform activity and decreased decomposition of the drug in the body. The majority of current studies were performed in-vitro system. The results could be questionable. Results from in vivo studies and clinical trials would provide stronger evidence and better advice for treating patients with both drugs and herbs simultaneously.
Furanocoumarins are the active ingredient in grapefruit juice (GFJ) inhibiting intestinal CYP3A4 and thereby increasing the passage of drugs, such as felodipine, with extensive intestinal first-pass metabolism (29). Chinese herbs that contain furanocoumarins include Qian Hu, Dang Gui, Chai Hu, Fang Feng, Du Huo, etc. Of them the inhibitory effect of Qian Hu on CYP1A1, 2E, 2C211, 2B, and the inhibitory effect of Bai Zhi on CYP2C, 3A, 2D1 have been confirmed (26,27). Although the effect of other herbs on CYP have not been confirmed in clinical or laboratory studies it may be advisable not to use these herbs
DIALOGHIDIMEDICINAINTEGRATA estate 2017