Prof.dr Radmila Veličković Radovanović Klinika za...
Transcript of Prof.dr Radmila Veličković Radovanović Klinika za...
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Prof.dr Radmila Veličković-Radovanović
Klinika za nefrologiju, KC Niš
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modalitet lečenja bolesnika u terminalnoj
fazi bubrežne insuficijencije
- otvoreni pristup peritoneumu
omogućava intraperitonealnu
primenu antibiotika kod boles-
nika na peritoneumskoj dijalizi
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CAPD vs. APDBioinkompatibilnost
(aminoglikozidi+beta laktami)
adekvatni režim doziranjaantibiotika
farmakoloski profil
Interakcije antibiotika
Kompatibilnost Stabilnost Hemijski sastav rastvora Temperatura
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Mera stabilnosti leka je brzina promena koje nastaju u doziranom obliku a koje mogu biti fizičke, hemijske i
mikrobiološke.
Sposobnost antimikrobnih lekova da u PD rastvorima zadrže
hemijske, fizičke, mikrobiološke, toksikološke i terapijske osobine pod definisanim uslovima čuvanja
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fizička
mikrobiološka
hemijska
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Temperatura
pH rastvora
Fotodegradacija
Vlaga
Lek-lek interakcija
Rastvor vankomicina-nizak pH (2,8-4,5)
u kombinaciji sa drugim supstancama, možepostati fizički ili hemijski nestabilan
Fish R. et al. Perit Dial Int. 2012;32(3):332-8.
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Hemijski sastav dijalizata utiče na brzinu difuzije, stabilnost i mikrobiolosku aktivnost antibiotika
(vankomicin, teikoplanin, aminoglikozidi, beta laktami, antimikotici)
Tobudic S.et all. Comparative in vitro antimicrobial activity of vancomycin, teicoplanin, daptomycin and ceftobiprole in four different peritoneal dialysis
fluids. Eur J Clin Microbiol Infect Dis. 2012
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Cefazolin, tobramicin, kotrimoxazol i vankomicin sustabilni u PD rastvorima 24 h
Amoxicilin, cefepim, ceftazidim i imipenem su manjestabilni (6h) i moraju se koristiti pažljivo
Stabilnost imipenema je samo 2 h u Physionealu i
6 h u Extranilu (žuta prebojenost rastvora).
Deslandes G, et al.. Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated
Peritoneal Dialysis Perit Dial Int. 2016
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Ceftazidim je stabilan
24 h u Extranealu
12 h u Physionealu 1.36% i
6 h u Physionealu 3.86%.
Deslandes G, et al.. Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated
Peritoneal Dialysis Perit Dial Int. 2016
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STABILNOST ANTIBIOTIKA U DIJALIZNIM RASTVORIMA
ZAVISNO OD TEMPERATURE
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Različita stabilnost antibiotika u zavisnosti od T
Stabilnost je najmanja na t - 37°C a najveća na 4°C
Gentamicin - 14 d na svim temperaturama
Vancomycin - 4 d na 37°C, 14 d na 25°C i 4°C
Cefazolin - 24 h na 37°C, 14 d na 4°C.
Ceftazidim 6 h na 37°C, 14 d na 4°C.
Ranganathan D, et all. Stability of antibiotics for intraperitoneal administration in extraneal7.5% icodextrin peritoneal dialysis bags. Perit Dial Int. 2015
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Silver S. Am J Nephrol 2014
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Ranganathan D, et all. Stability of antibiotics for intraperitoneal administration in extraneal7.5% icodextrin peritoneal dialysis bags. Perit Dial Int. 2015
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Premixed ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral PD solution is stable for at least 168 hours when refrigerated. Both the antibiotics are stable for at least 24 hours at 25 and 37°C, permitting storage at room temperature and pre-warming of PD bags to body temperature prior to its administration.
Stabilnost ceftazidima i cefazolinau PD rastvorima
Patel RP, et all. Stability of the combination of ceftazidime and cephazolin in icodextrinor pH neutral peritoneal dialysis solution. Perit Dial Int. 2014
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Influence of storage conditions and time on antibiotic concentration in dialysate as measured by HPLC.
This study supports the stability of cephazolin and cefepime in all three PD solutions.Antibiotic stability studies should ideally be conducted prior to registration and marketing of new PD solutions
Ranganathan D, et all. Stability of antibiotics for intraperitoneal administration in extraneal 7.5% icodextrin peritoneal dialysis bags. Perit Dial Int. 2015
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Vankomicin aplikovan u Extranilu
Da li čuvati u frižideru ili na sobnoj temperaturi?
rastvori su stabilni na temperaturi tela 24h.
Heparin smanjuje stabilnost vankomicina u rastvoru icodextrina
Preporuka je rastvore čuvati u frižideru(4C) ukoliko se ne koriste u toku 24h
Vancomycin in icodextrin peritoneal dialysis solution. Ann Pharmacother. 2006
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In PD patients, IV tigecycline has been used successfully to treat MRSA peritonitis.
Tigecycline has a large volume of distribution, resulting in high tissue concentrations but relatively low serum concentrations.
Biliary excretion is the primary route of elimination and no dosage adjustment is recommended in patients with renal impairment, including HD patients.
Tigecycline je stabilan u1.5% rastvoru dextroze i icodextrinu PDF at 4, 25 na 37°C
Antony S. Use of a novel antibiotic (tigecycline) in the treatment of peritoneal dialysis-associated MRSA peritonitis. Dial Transplant 2008.
Robiyanto Robiyanto, et all. Stability of Tigecycline in Different Types of Peritoneal Dialysis Solutions. Perit Dial Int. 2016.
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Antimicrob. Agents Chemother. 2012; 56 (7): 3992-3995.
Fosfomicin je stabilan u1.5% rastvoru dextroze iicodextrinu PDF at 4, 25 na 37°C
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Inkompatibilnost antibiotika je jedanod mogućih problema
farmakoterapije i predstavljaneželjenu reakciju koja se javlja
izmedju leka i rastvora ili drugog leka
a) gubitak ili smanjenje biološke aktivnosti leka,
b) povećanje njegove toksičnosti
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Fizička inkompatibilnost može da dovede do:
a) nepotpunog rastvaranja antibiotika
b) nepotpunog mešanja tečnosti
c) precipitacije zbog smanjenja rastvorljivosti
Hemijska reakcija može da se manifestuje
zamućenjem, stvaranjem precipitata i promenomboje rastvora
mnoge hemijske reakcije nisu manifestne
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Deslandes G, et al. Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied
to Automated Peritoneal Dialysis in The Pediatric Population. Perit Dial Int. 2016
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Deslandes G, et al. Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied
to Automated Peritoneal Dialysis in The Pediatric Population. Perit Dial Int. 2016
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Antibiotici pokazuju različitu stabilnost i kompatibilnost u rastvorima za PD
Racionalna i.p. primena antibiotika zahtevapoznavanje njihove stabilnosti i biokompatibilnosti u cilju efikasnog lečenja peritonitisa
Značaj adekvatnog čuvanja i primene PD rastvora za efikasnu i bezbednu i.p. aplikaciju antibiotika
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