Prof.dr Radmila Veličković Radovanović Klinika za ... · Mera stabilnosti leka je brzinapromena...

Prof.dr Radmila Veličković-Radovanović

Klinika za nefrologiju, KC Niš

modalitet lečenja bolesnika u terminalnoj

fazi bubrežne insuficijencije

- otvoreni pristup peritoneumu

omogućava intraperitonealnu

primenu antibiotika kod boles-

nika na peritoneumskoj dijalizi

CAPD vs. APDBioinkompatibilnost

(aminoglikozidi+beta laktami)

adekvatni režim doziranjaantibiotika

farmakoloski profil

Interakcije antibiotika

Kompatibilnost Stabilnost Hemijski sastav rastvora Temperatura

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

fizička

mikrobiološka

hemijska

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.

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

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

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

STABILNOST ANTIBIOTIKA U DIJALIZNIM RASTVORIMA

ZAVISNO OD TEMPERATURE

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

Silver S. Am J Nephrol 2014

Ranganathan D, et all. Stability of antibiotics for intraperitoneal administration in extraneal7.5% icodextrin peritoneal dialysis bags. Perit Dial Int. 2015

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

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

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

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.

Antimicrob. Agents Chemother. 2012; 56 (7): 3992-3995.

Fosfomicin je stabilan u1.5% rastvoru dextroze iicodextrinu PDF at 4, 25 na 37°C

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

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

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

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

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