Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data
Background While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5’-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. Methods We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. Results High intra-personal variability in raltegravir serum levels was seen. Comparable $ C_{max} $ concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While $ C_{max} $ seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased $ AUC_{12} $ is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. Conclusions We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
AIDS research and therapy - 12(2015), 1 vom: 17. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Spinner, Christoph D [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| Anmerkungen: |
© Spinner et al.; licensee BioMed Central. 2015 |
|---|
| doi: |
10.1186/s12981-014-0041-8 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
SPR029203619 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR029203619 | ||
| 003 | DE-627 | ||
| 005 | 20230519185553.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201007s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12981-014-0041-8 |2 doi | |
| 035 | |a (DE-627)SPR029203619 | ||
| 035 | |a (SPR)s12981-014-0041-8-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Spinner, Christoph D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © Spinner et al.; licensee BioMed Central. 2015 | ||
| 520 | |a Background While HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5’-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power. Methods We report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used. Results High intra-personal variability in raltegravir serum levels was seen. Comparable $ C_{max} $ concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While $ C_{max} $ seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased $ AUC_{12} $ is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels. Conclusions We found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations. | ||
| 650 | 4 | |a HIV |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chewed |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Raltegravir |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Mycobacterium avium |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Pharmacokinetic |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Wille, Florian |4 aut | |
| 700 | 1 | |a Schwerdtfeger, Christiane |4 aut | |
| 700 | 1 | |a Thies, Philipp |4 aut | |
| 700 | 1 | |a Tanase, Ursula |4 aut | |
| 700 | 1 | |a Von Figura, Guido |4 aut | |
| 700 | 1 | |a Schmid, Roland M |4 aut | |
| 700 | 1 | |a Heinz, Werner J |4 aut | |
| 700 | 1 | |a Klinker, Hartwig Hf |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t AIDS research and therapy |d London : BioMed Central, 2004 |g 12(2015), 1 vom: 17. Jan. |w (DE-627)SPR029199905 |w (DE-600)2173450-1 |x 1742-6405 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2015 |g number:1 |g day:17 |g month:01 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1186/s12981-014-0041-8 |z kostenfrei |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_SPRINGER | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2015 |e 1 |b 17 |c 01 | ||