Behaviours of Drugs in the Milk - A Review

Yıl 2018, Cilt: 13 Sayı: 3, 364 - 372, 25.12.2018

Zeynep Özdemir Bünyamin Traş

https://doi.org/10.17094/ataunivbd.319443

Öz

Milk is a food containing many biologically active substances that have an important place in the nourishment of

newborns and adults. The transition of the drugs used in the treatment, as well as the environmental pollutants to milk cause

a potential risk for consumer health as well as economical losses due to exceed of the legal limits of these compounds set by

authorities. The transition of these chemicals to milk is complex; while active transport and passive diffusion play were found

to have an important role. The transition abilities of the drugs into milk are defined by milk/plasma ratio. The M/P ratios of

the drugs are affected by the composition of the milk and the physicochemical properties of the drug. The concentration of

the drugs in the milk depends on the factors of the drug (protein binding, ionization, molecular weight, lipophilicity, drugdrug

and drug-nutrient interactions) and organism (race, species, lactation period, parity, disease and nutrition). If the

transition properties of the compounds of concern are known or able to be modelized in kinetic applications, it can be useful

for preventing milk from drug residues.The success of mastitis treatment depends on the proper use of drugs and knowing

of the behaviour of drugs in the milk.

Anahtar Kelimeler

Behaviour, Drug, Factor, Milk, Transition

İlaçların Sütteki Davranışları - Derleme

Öz

Süt, yeni doğanlar ve yetişkinlerin beslenmesinde önemli yeri olan birçok biyolojik aktif madde içeren bir besindir. İnsan

ve hayvanların tedavisinde kullanılan ilaçların ve çevresel kirleticilerin süte geçme yeteneği, sütü sağlık ve ekonomik açıdan

sorunlu hale getirmektedir. Kaliteli ve güvenli gıda üretimine yönelik yasal ve bilimsel uygulamalar bu sorunları önlemeyi

amaçlamaktadır. Aktif transport ve pasif difüzyon, ilaçların süte geçişinde önemli rol oynamakla birlikte diğer mekanizmaların

da etkin olduğu bilinmektedir. İlaçların süte geçişlerisüt/plazma oranı ile belirlenir. Süt/plazma oranı sütün bileşiminden ve

ilacın fizikokimyasal özelliklerinden etkilenir. Sütteki ilaç konsantrasyonu, ilaca (proteine bağlama, iyonizasyon, molekül

ağırlığı, lipofiliklik, ilaç-ilaç ve ilaç-besin etkileşimi) ve canlıya (ırk, tür, laktasyon periyodu, doğum sayısı, hastalık ve beslenme)

bağlı olarak değişiklik gösterir. Söz konusu bileşiklerin geçiş özelliklerinin bilinmesi veya kinetik uygulamalarla

modellenebilmesi sütte ilaç kalıntılarının önlenmesinde faydalı olabilir. Mastitis tedavisinin başarısı, ilaçların doğru

kullanılması ve ilaçların sütteki davranışlarının bilinmesine bağlıdır.

Anahtar Kelimeler

Davranış, Faktör, Geçiş, İlaç, Süt

Kaynakça

• Cheah Y., Kuhn RJ., 1995. Active transport of cimetidine into human milk. Clin Pharmacol Ther, 58, 548-555.
• Gerk PM., Kuhn RJ., Desai NS., McNamara PJ., 2001. Active transport of nitrofurantoin into human milk. Pharmacotherapy, 21, 669-675.
• Schadewinkel‐Scherkl AM., Rasmussen F., Merck CC., Nielsen P., Frey HH., 1993. Active Transport of Benzylpenicillin Across the Blood‐Milk Barrier. Pharmacology & Toxicology, 73, 14-19.
• Gerk PM., Hanson L., Neville MC., McNamara PJ., 2002. Sodium dependence of nitrofurantoin active transport across mammary epithelia and effects of dipyridamole, nucleosides, and nucleobases. Pharmacol Res, 19, 299-305.
• Ito S., Alcorn J., 2003. Xenobiotic transporter expression and function in the human mammary gland. Advanced Drug Delivery Reviews, 55, 653-665.
• Jonker JW., Merino G., Musters S., van Herwaarden AE., Bolscher E., et al., 2005. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med, 11,127-129.
• Pulido MM., Molina AJ., Merino G., Mendoza G., Prieto JG., Alvarez AI., 2006. Interaction of enrofloxacin with breast cancer resistance protein (BCRP/ABCG2): influence of flavonoids and role in milk secretion in sheep. J Vet Pharmacol Ther, 29, 279-287.
• Otero JA., Real R., de la Fuente Á., Prieto JG., Marqués M., et al., 2013. The bovine ATP-binding cassette transporter ABCG2 Tyr581Ser single-nucleotide polymorphism increases milk secretion of the fluoroquinolone danofloxacin. Drug Metab Dispos, 41, 546-549.
• Otero J., Miguel V., González-Lobato L., García-Villalba R., Espín J., et al., 2016. Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid. Animal, 10, 238-247.
• Weikard R., Widmann P., Buitkamp J., Emmerling R., Kuehn C., 2012. Revisiting the quantitative trait loci for milk production traits on BTA6. Anim Genet, 43, 318-323.
• Barrera B., González-Lobato L., Otero JA., Real R., Prieto JG., et al., 2013. Effects of triclabendazole on secretion of danofloxacin and moxidectin into the milk of sheep: Role of triclabendazole metabolites as inhibitors of the ruminant ABCG2 transporter. The Veterinary Journal, 198, 429-436.
• Otero J., García-Mateos D., de la Fuente A., Prieto J., Álvarez A., Merino G., 2016. Effect of bovine ABCG2 Y581S polymorphism on concentrations in milk of enrofloxacin and its active metabolite ciprofloxacin. J Dairy Sci, 99, 5731-5738.
• van Herwaarden AE., Schinkel AH., 2006. The function of breast cancer resistance protein in epithelial barriers, stem cells and milk secretion of drugs and xenotoxins. Trends Pharmacol Sci, 27, 10-16.
• Tras B., 2016. Kedi ve Köpeklerde Davranış Bozuklukları. 2nd ed., 359, Olgun-Çelik Ofset Matbaa Ltdi Sti., Konya.
• Karapehlivan M., Atakisi E., Atakisi O., Yucayurt R., Pancarci S., 2007. Blood biochemical parameters during the lactation and dry period in Tuj ewes. Small Ruminant Research, 73, 267-271.
• Santschi E., Papich M., 2000. Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation. J Vet Pharmacol Ther, 23, 359-363.
• Ambros L., Montoya L., Kreil V., Waxman S., Albarellos G., et al., 2007. Pharmacokinetics of erythromycin in nonlactating and lactating goats after intravenous and intramuscular administration. J Vet Pharmacol Ther, 30, 80-85.
• Carceles C., Diaz M., Vicente M., Sutra J., Alvinerie M., Escudero E., 2001. Milk kinetics of moxidectin and doramectin in goats. Res Vet Sci, 70, 227-231.
• Imperiale FA., Mottier L., Sallovitz JM., Lifschitz AL., Lanusse CE., 2003. Disposition of doramectin milk residues in lactating dairy sheep. J Agric Food Chem, 51, 3185-3190.
• Shem-Tov M., Ziv G., Glickman A., Saran A., 1997. Pharmacokinetics and penetration of danofloxacin from the blood into the milk of ewes. Vet Res, 28, 571-580.
• Shem-Tov M., Rav‐Hon O., Ziv G., Lavi E., Glickman A., Saran A., 1998. Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows. J Vet Pharmacol Ther, 21, 209-213.
• Gehring R., Smith G., 2006. An overview of factors affecting the disposition of intramammary preparations used to treat bovine mastitis. J Vet Pharmacol Ther, 29, 237-241.
• Mestorino N., Errecalde JO., 2012. Pharmacokinetic-pharmacodynamic considerations for bovine mastitis treatment. A Bird’s Eye View of Veterinary Medicine, 22, 423-472.
• Burmanczuk A., Rolinski Z., Kowalski C., Zan R., 2011. Concentration of cefacetril in milk after its intramammary administration to cows with healthy and inflammed mammary gland. Bull Vet Inst Pulawy, 55, 685-658.
• Sezgin A., Tras B., 2016. Effects of mastitis on pharmacokinetics of elimination with milk of benzimidazole anthelmintics. British Journal of Pharmacology and Toxicology, 7, 31-35.
• Kissell LW., Leavens TL., Baynes RE., Riviere JE., Smith GW., 2015. Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis. J Am Vet Med Assoc, 246, 118-125.
• Gips M., Soback S., 1999. Norfloxacin pharmacokinetics in lactating cows with sub‐clinical and clinical mastitis. J Vet Pharmacol Ther, 22, 202-208.
• Yagdiran Y., Tallkvist J., Artursson K., Oskarsson A., 2016. Staphylococcus aureus and lipopolysaccharide modulate gene expressions of drug transporters in mouse mammary epithelial cells correlation to inflammatory biomarkers. PloS One, 11, e0161346.
• Oskarsson A., Yagdiran Y., Nazemi S., Tallkvist J., Knight C., 2017. Short communication: Staphylococcus aureus infection modulates expression of drug transporters and inflammatory biomarkers in mouse mammary gland. J Dairy Sci, 100, 1-6.
• Kumar S., Srivastava AK., Dumka V., Kumar N., Raina RK., 2010. Plasma pharmacokinetics and milk levels of ceftriaxone following single intravenous administration in healthy and endometritic cows. Vet Res Commun, 34, 503-510.
• Martinez M., Modric S., 2010. Patient variation in veterinary medicine: part I. Influence of altered physiological states. J Vet Pharmacol Ther, 33, 213-226.
• Merino G., Perez M., Real R., Egido E., Prieto JG., Alvarez AI., 2010. In vivo inhibition of BCRP/ABCG2 mediated transport of nitrofurantoin by the isoflavones genistein and daidzein: A comparative study in Bcrp1−/− Mice. Pharm Res, 27,2098-2105.
• Elmas M., Tras B., Bas A., Nizamlioglu F., Colak M., Yapar K., 1999. Disposition and milk levels of sulfadiazine-trimethoprim combination following intrauterine bolus administration in lactating cows during postpartum. Revue Med Vet, 150, 891-894.
• Agatonovic-Kustrin S., Ling L., Tham S., Alany R., 2002. Molecular descriptors that influence the amount of drugs transfer into human breast milk. J Pharm Biomed Anal, 29, 103-119.
• Tras B., Bas AL., Dinc DA., 1994. A pharmacodynamic study on the ion-trapping phenomena in udder tissues of cows. Turk J Vet Anim Sci, 18, 157-159.
• Sisodia C., Stowe C., 1964. The mechanism of drug secretion into bovine milk. Annals of the New York Academy of Sciences, 111, 650-661.
• Antonić J., Grabnar I., Milčinski L., Škibin A., Süssinger A., et al., 2011. Influence of P-glycoprotein inhibition on secretion of ivermectin and doramectin by milk in lactating sheep. Vet Parasitol, 179, 159-166.
• Real R., Egido E., Perez M., Gonzalez‐Lobato L., Barrera B., et al., 2011. Involvement of breast cancer resistance protein (BCRP/ABCG2) in the secretion of danofloxacin into milk: interaction with ivermectin. J Vet Pharmacol Ther, 34, 313-321.
• El-Sooud KA., 2003. Influence of albendazole on the disposition kinetics and milk antimicrobial equivalent activity of enrofloxacin in lactating goats. Pharmacol Res, 48, 389-395.
• Perez M., Real R., Mendoza G., Merino G., Prieto J., Alvarez A., 2009. Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones1. J Vet Pharmacol Ther, 32, 498-502.
• Perez M., Otero JA., Barrera B., Prieto JG., Merino G., Alvarez AI., 2013. Inhibition of ABCG2/BCRP transporter by soy isoflavones genistein and daidzein: effect on plasma and milk levels of danofloxacin in sheep. The Veterinary Journal, 196, 203-208.
• van Herwaarden AE., Wagenaar E., Merino G., Jonker JW., Rosing H., et al., 2007. Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. Mol Cell Biol, 27, 1247-1253.
• Manzini L., Halwachs S., Girolami F., Badino P., Honscha W., Nebbia C., 2017. Interaction of mammary bovine ABCG2 with AFB1 and its metabolites and regulation by PCB 126 in a MDCKII in vitro model. J Vet Pharmacol Ther, 1-8.
• Wassermann L., Halwachs S., Baumann D., Schaefer I., Seibel P., Honscha W., 2013. Assessment of ABCG2-mediated transport of xenobiotics across the blood–milk barrier of dairy animals using a new MDCKII in vitro model. Arch Toxicol, 87, 1671-1682.
• Mahnke H., Ballent M., Baumann S., Imperiale F., von Bergen M., et al., 2016. The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows. Drug Metab Dispos, 44, 700-708.