Pathways

Cinoxacin is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Cinoxacin passes through the liver and is then excreted from the body mainly through the kidney.

Ciprofibrate is a lipid-lowering fibrate used in the management of hyperlipidaemia. Ciprofibrate acts in the nucleus where is activates the peroxisome proliferator-activated receptor alpha (PPARα). PPARα binds to the retinoic acid receptor alpha (RXRα). This PPARα-RXRα complex regulate gene transcription/translation of proteins and enzymes involved lipolysis, fatty acid transport and biosynthesis, vLDL and HDL synthesis. Fatty acid biosynthesis is decreased due to the decrease expression of the enzyme acetyl-coA carboxylase. This enzyme is involved in one of the first steps in fatty acid synthesis by converting acetyl-coA to malonyl coA. Fatty acid uptake from the plasma into the liver is increased. This is because there is an upregulation of the fatty acid transporter. This decreases the amount of circulating fatty acids. Fatty acid metabolism is also increased due to upregulation of acyl coA synthase, an enzyme involved in fatty acid oxidation. These 3 alterations ultimately decrease fatty acids in the body, making less fatty acids available for triglyceride synthesis. Ciprofibrate also increases HDL synthesis by upregulating apolipoprotein A1 (APOA1) and apolipoproteins A2 (APOA2), which forms part of HDL. HDL is considered good cholesterol. VLDL and LDL are considered bad cholesterol. These levels are decreased due to downregulation of APOB which forms part of triglyceride-rich vLDL and LDL. Finally, triglyceride levels are decreased by 30%-60% via upregulation of lipoprotein lipase (LPL). LPL hydrolyses triglyceride, thus breaking it down. Other proteins that affect LPL are also altered. For instance, APOA5 activates LPL and it’s expression is increased with ciprofibrate. APOC3 inhibits lipolysis by inhibiting LPL, therefore, ciprofibrate decreases the expression of APOC3. Overall, ciprofibrate lowers LDL-C, total-C, triglycerides, and Apo B, while increasing HDL-C.

Cipofloxacin is a second generation fluoroquinolone antibacterial active against gram-negative and gram-positive bacteria. Cipofloxacin inhibits DNA gyrase (topoisomerase II) and topoisomerase IV. These proteins prevent supercoiling in bacterial DNA. The inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV causes supercoiling of the bacterial DNA. This prevents DNA replication.

Metabolites of Ciprofloxacin are predicted with biotransformer.

The nuclear entry of clock gene products is required to establish the negative feed back loop- a key step in proper circadian rhythm. Heterodimerization of clock proteins PER and CRY is required for translocation to the nucleus. Nuclear entry of PER can be regulated by mammalian casein kinase I (CK1). Once in the nucleus, PER and CRY proteins appear to differentially inhibit the transactivation by CLOCK/BMAL1. Proteins like REV-ERBa and DEC also regulate the transcriptional activation by CLOCK/BMAL1. In addition, CRY, PER, and BMAL1-CLOCK play bidirectional roles in transcription resulting in interactivating feedback loops. The expression of BMAL1 and CLOCK can be upregulated by CRY and PER. Such loops are believed to be important in the stability and persistence of circadian rhythm.